Comprehensive Immunology Notes: Antibody Structure, T Cells, MHC, and Antigen Presentation

Antibody Structure and Immunoglobulin Classes

  • Antigen: any foreign molecule or part of a molecule that, when introduced into the body, triggers the production of an antibody by the immune system.
  • Antibody: a secreted antibody has the same general Y-shaped structure as a B-cell receptor but lacks the trans-membrane region that would anchor it to the plasma membrane.
  • Antigen-binding sites: located at the tips of the Y arms; these sites determine the antibody’s ability to identify a specific antigen.
  • Fc tail: formed by the constant (C) regions of the Heavy (H) chains; determines the antibody’s distribution in the body and the mechanisms of antigen disposal.
  • Five major heavy-chain constant regions define five antibody classes (isotypes). Names are based on the alternative term for antibody, Immunoglobulin (Ig): IgM, IgA, IgG, IgE, IgD.
  • Polymerization patterns:
    • IgM is primarily a pentamer (polymerized form).
    • IgA is primarily a dimer.
    • IgG, IgE, and IgD exist predominantly as monomers.
  • Structure highlights:
    • The antibody is composed of two identical heavy chains and two identical light chains.
    • There are two antigen-binding sites per antibody, yielding potential bivalent binding.
    • The class (IgM, IgA, IgG, IgE, IgD) is defined by the Heavy Chain Constant Regions (CH).
  • J chain and secretory component:
    • IgM and IgA contain a J chain, which helps hold subunits together.
    • IgA acquires a secretory component as it is secreted across mucous membranes, protecting it from enzymatic cleavage.
  • IgG details:
    • IgG is the most abundant class in blood and tissue fluids.
    • IgG crosses the placenta and confers passive immunity to the fetus.
    • IgG has several subclasses: IgG1, IgG2, IgG3, and IgG4.
    • All four subclasses cross the placenta.
  • IgM, IgA, IgE, IgD distinct features:
    • IgM is the first class produced after initial exposure to antigen.
    • IgA is found in secretions (tears, saliva, mucus, breast milk) and has a secretory component.
    • IgE is involved in allergic responses and defense against parasites; it triggers mediator release from mast cells and basophils; has a short half-life.
    • IgD is primarily on the surface of naive B cells as an antigen receptor; has a shorter half-life.
  • Immunoglobulin domains and chain organization:
    • Each light chain has two Immunoglobulin Domains (IGD): Variable (VL) and Constant (CL).
    • Each heavy chain has four IGDs: Variable (VH) and Constant (CH1, CH2, CH3).
    • The VL–CL and VH–CH1–CH2–CH3 arrangements form the complete Ig molecule.
  • Summary takeaway: antibody class is defined by heavy chain constant regions; the molecule’s architecture supports diverse antigen recognition, distribution, and effector functions across the body.

Immunoglobulin Molecules: Heavy and Light Chains

  • IgG antibodies are large molecules with a molecular weight of ~150 extkDa150 \, ext{kDa} and are composed of two different polypeptide chains:
    • One heavy chain (H) of ≈50 extkDa50 \, ext{kDa}
    • One light chain (L) of ≈25 extkDa25 \, ext{kDa}
  • Each IgG molecule consists of 2 heavy chains and 2 light chains; the two Heavy Chains and the two Light Chains are identical within a given IgG, giving two identical antigen-binding sites.
  • Light-chain types: two types exist—kappa (κ) and lambda (λ). An antibody has either κ chains or λ chains, never both. The κ:λ ratio in humans is about 2:1.
  • Heavy-light chain linkage: the heavy and light chains are linked to each other by disulfide bonds (–S–S–).
  • Relative molecular weights: heavy chain ≈50 kDa50 \,\text{kDa}, light chain ≈25 kDa25 \,\text{kDa}; two of each per IgG molecule.
  • Domain organization (reiterated): LC has VL and CL IGDs; HC has VH and CH1, CH2, CH3 IGDs.
  • Implication: identical HC and LC yield two identical antigen-binding sites, enabling bivalent binding and cross-linking of antigens.

The Five Classes of Immunoglobulins (Isotypes)

  • IgM: first class produced after initial antigen exposure; pentameric form in circulation; plays a key role in agglutination and early defense.
  • IgA: primarily a dimer in secretions; contains a J chain; secretory component attaches to protect from cleavage; crucial for mucosal immunity.
  • IgG: most abundant in serum; monomer; crosses the placenta; performs neutralization, opsonization, complement activation; several subclasses: IgG1, IgG2, IgG3, IgG4.
  • IgE: monomer; binds to mast cells and basophils; triggers histamine release; important in defense against parasites and allergic reactions; short half-life.
  • IgD: monomer; primarily serves as an antigen receptor on naive B cells; short half-life.
  • J chain and secretory component:
    • IgM and IgA contain a J chain (linking subunits).
    • IgA acquires a secretory component during secretion across mucosal surfaces.
  • Subclass details (IgG):
    • IgG is the most abundant Ig in serum and tissues; IgG1–IgG4 are subclasses with variations in interchain disulfide bonds and tissue distribution.
    • All IgG subclasses cross the placenta (providing fetal immunity).

IgG Subclasses: Structure, Abundance, and Half-Life

  • Normal serum composition:
    • IgG1: ~60–70% of total IgG
    • IgG2: ~20–30%
    • IgG3: ~5–8%
    • IgG4: ~1–4%
  • Half-lives:
    • IgG3: ~7–8 days (more susceptible to proteolysis)
    • IgG1, IgG2, IgG4: ~21–24 days
  • Functions of IgG subclasses: neutralization, opsonization, complement activation, antibody-dependent cellular cytotoxicity (ADCC).

Structure of the Immunoglobulin Molecule

  • Overall architecture: three globular regions (two antigen-binding arms and a flexible hinge) connected by a hinge region.
  • Antigen-binding sites: located at the tips of the two Fab arms; responsible for recognizing specific epitopes.
  • Hinge region: provides flexibility allowing binding to nearby or distant epitopes and to bacterial surface structures.
  • Fab fragment schematic: contains the variable regions that form the antigen-binding site.
  • Terminology:
    • N-terminus: amino terminus of the polypeptide.
    • C-terminus: carboxy terminus.

Antibody Flexibility and Hapten Binding

  • Flexibility is evident in antibody–hapten interactions: hapten (small molecule) attached to a carrier can form dimers, trimers, tetramers with anti-hapten antibodies, observable by electron microscopy.
  • Implication: antibody hinge flexibility enables binding to repetitive epitopes on pathogens and interaction with effector molecules.
  • Hapten definition: a small molecule that elicits an immune response only when attached to a large carrier such as a protein; the carrier may be immunogenic itself.

Immunoglobulin Domains and Antibody Folding

  • Domains: Constant (C) and Variable (V) domains in Ig molecules.
  • Light chain domains: VL and CL; Heavy chain domains: VH and CH1–CH3.
  • Ig domain structure: barrel-like fold with two beta-sheets forming the core; stabilized by a disulfide bond.
  • Variability concentrated in the V domain loops, forming the antigen-binding site.

Antigen Binding: Variability and CDRs

  • Localized hypervariable regions form the antigen-binding site.
  • Heavy- and light-chain V regions differ between antibodies: sequence variability is concentrated in hypervariable regions.
  • Hypervariable regions: HV1, HV2, HV3 (also called CDR1, CDR2, CDR3).
  • Framework regions (FR1–FR4) flank the HV regions and provide structural stability.
  • HV3 (CDR3) is the most variable part of the domain.
  • The combination of HV loops from both heavy and light chains forms a single antigen-binding surface at each Fab arm tip.

Binding Site Morphology: Pockets, Grooves, and Surfaces

  • Types of Fab-binding sites: pockets, grooves, extended surfaces, and protruding surfaces.
  • Small antigens (hapten or short peptides) typically bind in pockets or grooves between heavy and light chain V domains.
  • Large protein antigens may form extended interfaces that involve all CDRs and sometimes parts of the framework regions.
  • Some Abs with elongated CDR3 loops can project a finger into recessed regions of the antigen.

Antigen Shape and Epitope Concepts

  • Antigen-binding specificity is directed to defined regions on antigen surfaces called epitopes (antigen determinants).
  • Epitopes can be continuous/linear (a single stretch of polypeptide) or conformational/discontinuous (brought together by folding).
  • Conformational epitopes may involve amino acids from different parts of the protein that are juxtaposed in the folded protein.

Antigen–Antibody Interactions: Forces and Reversibility

  • Interactions are non-covalent and can be disrupted by:
    • High salt concentrations
    • Changes in pH
    • Detergents
    • Competition with excess free epitope
  • Binding is reversible and non-covalent.

T-Cell Receptors: Fab-like Structure and Antigen Recognition

  • T-cell receptor (TCR) is structurally similar to a Fab fragment.
  • TCR recognizes foreign peptides displayed by self MHC molecules (peptide–MHC complex).
  • TCR is a heterodimer composed of two different chains:
    • TCRα and TCRβ, linked by a disulfide bond.
  • Each TCR has a single antigen-binding site and is not secreted.
  • Each chain has an N-terminal variable (V) region and a constant (C) region; the chains carry carbohydrate side chains.
  • The extracellular portion comprises two domains per chain, resembling immunoglobulin V and C domains.
  • The transmembrane helices contain positively charged residues that anchor the receptor in the membrane.

T-Cell Recognition of Antigens: Peptide + MHC Complexes

  • T-cells respond to short amino-acid sequences (peptides) derived from intracellular pathogens.
  • Peptides are delivered to the cell surface by MHC molecules:
    • MHC class I presents cytosolic peptides to CD8+ cytotoxic T-cells.
    • MHC class II presents vesicular/ extracellular peptides to CD4+ helper T-cells.
  • Differences in TCR recognition between antibodies and TCR: antibodies bind to epitopes on protein surfaces; TCRs recognize peptide fragments bound to MHC, not necessarily exposed on the protein surface.
  • When a TCR recognizes a peptide–MHC complex, it initiates T-cell activation and downstream immune responses.

MHC Molecules: Classes I and II

  • MHC molecules are transmembrane glycoproteins encoded by the Major Histocompatibility Complex (MHC).
  • Two classes exist with distinct subunit composition but similar overall architecture:
    • MHC I: α chain (MW ≈ 43 kDa) associated with β2-microglobulin (β2m, MW ≈ 12 kDa).
    • MHC II: two transmembrane chains, α (≈34 kDa) and β (≈20 kDa), each with two domains.
  • Structural similarity: both have Ig-like domains in the regions proximal to the membrane; the distal domains form the peptide-binding groove.
  • MHC I groove is formed by α1 and α2 domains; peptide binds within this long groove; the α3 domain and β2m resemble Ig C domains and provide structural support.
  • The peptide-binding groove in MHC I is closed at both ends, typically binding short peptides (8–10 aa).
  • The peptide-binding groove in MHC II is open at both ends, allowing longer peptides (often ≥13 aa) to bind and extend beyond the groove.
  • The peptide–MHC surface is what T cells recognize via their TCRs (CD4 or CD8 co-receptors bind outside the peptide-binding site).

Features of MHC Polymorphism and Gene Organization

  • MHC is highly polymorphic and polygenic:
    • Each person expresses multiple MHC class I and II molecules (at least three of each are typical).
    • High allelic diversity across the population ensures broad pathogen antigen presentation.
  • Codominant expression: both maternal and paternal alleles are expressed and presented.
  • Major MHC regions include class I genes (e.g., HLA-A, HLA-B, HLA-C) and class II genes (e.g., DR, DP, DQ), plus genes involved in antigen processing (e.g., TAP1, TAP2, LMPs) and HLA-DM.
  • DRα locus is an exception to some polymorphism patterns (functionally monomorphic in some contexts).
  • The MHC genetic organization is conserved across humans (HLA) and mouse (H2). Class III genes encode complement proteins and cytokines (e.g., C4, C2, factor B, TNF family).

Peptide Binding and Presentation by MHC I and II

  • MHC I: binds short peptides (8–10 aa) via a network of hydrogen bonds and ionic interactions at peptide ends; mostly anchored at the termini.
  • MHC II: binds longer peptides; no strict end-anchoring pattern; peptide extends along the groove.
  • Peptide presentation on MHC surfaces is the key signal for T-cell recognition.

Antigen Processing and Presentation Pathways

  • Antigen processing and presentation involve two main intracellular compartments:
    1) Cytosol: peptides from cytosolic proteins are processed and presented by MHC class I to CD8 T cells.
    2) Vesicular system (ER, Golgi, endosomes, lysosomes): peptides from endocytic/vesicular pathways are processed and presented by MHC class II to CD4 T cells.
  • Antigen presentation involves a complex trafficking system for generating peptides and loading them onto MHC molecules.
  • The generation of TCR ligands (peptide–MHC complexes) depends on antigen processing and the appropriate MHC presentation pathway.
  • Cross-presentation: some exogenous antigens taken up by APCs can be processed and presented on MHC class I to CD8 T cells.

The Peptide-Loading Complex and Viral Evasins

  • For MHC I, peptides are loaded in the endoplasmic reticulum (ER) via TAP (Transporters associated with Antigen Processing): TAP1 and TAP2 form a heterodimer that transports peptides into the ER lumen.
  • The peptide loading involves a complex including tapasin, calreticulin, and ERp57; MHC I is retained in the ER until a suitable peptide binds.
  • Viral immunoevasins can disrupt antigen presentation by interfering with peptide loading, transport, or MHC stability:
    • HSV-1 ICP47 inhibits TAP peptide transport.
    • HCMV US6 inhibits TAP ATPase activity.
    • Adenovirus E19 retains MHC I in the ER by competing with tapasin.
    • Certain viral proteins (e.g., mK3) cause ubiquitin-mediated degradation of MHC I.
    • US11 promotes dislocation of nascent MHC I to the cytosol for degradation.
  • The peptide-loading complex can be targeted by viral immunoevasins, illustrating pathogen strategies to evade T cell responses.

Invariant Chain and CLIP in MHC Class II

  • Invariant chain (Ii) directs newly synthesized MHC class II molecules to acidified endocytic vesicles and blocks peptide binding in the ER and during transport.
  • Ii associates as trimers with MHC II α:β heterodimers; CLIP (class II-associated invariant chain peptide) occupies the peptide-binding groove after Ii cleavage.
  • Ii is cleaved progressively in acidified vesicles, ultimately leaving CLIP bound to MHC II.
  • CLIP must be displaced to allow antigenic peptides to bind MHC II for surface presentation.

HLA-DM and Peptide Loading onto MHC II

  • HLA-DM facilitates the exchange of CLIP for antigenic peptides on MHC II in the endosomal/MIIC compartments.
  • HLA-DM is essential for proper peptide loading and presentation by MHC II across professional APCs (dendritic cells, macrophages, B cells).
  • HLA-DM genes reside in the MHC II region; HLA-DM acts as a peptide editor rather than a peptide-binding molecule.

Antigen-Presenting Cells (APCs)

  • Dendritic cells (DCs) are distributed throughout lymph nodes and tissues; they are the most potent activators of naive T cells.
  • Macrophages are distributed in lymph nodes (marginal sinus, medullary cords) and play roles in presenting antigens and phagocytosis.
  • B cells are concentrated in follicles and can present soluble antigen to CD4 T cells after internalization and processing via MHC II.
  • APCs differ in:
    • Modes of antigen uptake (receptor-mediated endocytosis, phagocytosis, macropinocytosis)
    • Levels of MHC II and co-stimulatory molecules (e.g., B7 family)
    • Expression of adhesion molecules (e.g., DC-SIGN, CD58)
    • Anatomical location and the type of antigen presented effectively
  • Dendritic cells can be categorized into conventional dendritic cells (cDC) and plasmacytoid dendritic cells (pDC):
    • cDC are strong activators of naive T cells.
    • pDC produce large amounts of interferons in response to viral infections.
  • Dendritic cells can be identified by surface markers such as CD11c and BDCA-2 (CD303).
  • Langerhans cells (skin DCs): immature cells that take up antigen and migrate to lymph nodes, where they differentiate into mature DCs capable of priming naive T cells.

Naive T-Cell Activation in Lymph Nodes

  • Naive T cells recirculate through peripheral lymphoid organs (lymph nodes) entering via high endothelial venules (HEVs).
  • Entry is guided by chemokines and adhesion molecules; T cells encounter mature dendritic cells presenting antigen.
  • If a T cell does not encounter its specific antigen, it receives survival signals and exits via lymphatics.
  • If a T cell recognizes its antigen, it becomes activated, proliferates, and differentiates into effector T cells.
  • After expansion, antigen-specific effector T cells exit lymph nodes and re-enter circulation in large numbers.

T-Cell Activation Signals

  • Signal 1: T-cell receptor (TCR) recognition of a peptide–MHC complex on an APC.
  • Signal 2: Costimulatory signal, commonly provided by B7 molecules (CD80/CD86) on APCs binding to CD28 on T cells, enhancing survival and proliferation.
  • Signal 3: Cytokines produced by APCs or the environment direct differentiation of naive T cells into distinct effector subsets (e.g., TH1, TH2, TH17, TFH, Treg).
  • In the absence of signal 3, regulatory pathways (e.g., TGF-β with low IL-6/IFN-γ/IL-12) can favor regulatory T cell development (FoxP3+ Tregs).

CD4 and CD8 Co-receptors in T-Cell Activation

  • CD8 recognizes MHC class I molecules; CD4 recognizes MHC class II molecules.
  • Co-receptors associate with the TCR–peptide–MHC complex to stabilize binding and enhance signaling.
  • CD4: a single-chain molecule with four immunoglobulin-like domains; D1–D2 form a rigid rod; D3–D4 form another rigid segment; D1 binds MHC II mostly.
  • CD8: a disulfide-linked heterodimer of α and β chains; each chain has a single Ig-like domain; anchors to the membrane via a polypeptide segment.
  • Co-receptors are essential for an effective T-cell response and are integral to MHC restriction.

MHC Restriction and T-Cell Recognition

  • T-cell recognition of antigens is MHC-restricted: a T cell specific for a given peptide bound to one MHC allele will not recognize the same peptide bound to a different MHC allele or a different peptide on the same MHC.
  • This restriction can arise from direct TCR–MHC contact or indirect effects of MHC polymorphism on peptide binding and conformation.

Superantigens: A Special Class of T-Cell Stimulators

  • Superantigens stimulate a large proportion of T cells by binding outside the conventional peptide–MHC recognition site, targeting the Vβ region of TCRs and the outer faces of MHC II.
  • They do not require processing into peptides; they bypass normal antigen processing and cause massive cytokine release.
  • Consequences: systemic toxicity and suppression of the adaptive immune response, aiding pathogenicity.
  • Examples: Staphylococcal enterotoxins (SE) and Toxic Shock Syndrome Toxin-1 (TSST-1).

Effector T-Cell Subsets and Their Roles

  • CD8 cytotoxic T cells (CTLs): kill target cells displaying peptide–MHC I; mechanisms include cytotoxic granules (perforin and granzymes) leading to apoptosis; Fas–FasL interactions also contribute.
  • CD4+ helper T cells differentiate into several subsets, each with distinct roles:
    • TH1: activate macrophages (via IFN-γ); help B cells (via CD40L) and support IgG production; promote cellular immunity.
    • TH2: support humoral responses; promote B-cell differentiation and isotype switching to IgE and certain IgG subclasses; help in parasitic defense and allergies.
    • TH17: recruit neutrophils and promote early inflammatory responses; secrete IL-17 family cytokines and IL-6.
    • TFH (T follicular helper) cells: help B cells in germinal centers to produce antibodies and undergo class switching; cytokines profile reflects TH1/TH2 patterns.
    • Treg (regulatory T cells): suppress immune responses to prevent autoimmunity and limit immunopathology.
  • T-cell differentiation signals (Signal 3) shape effector fate and are influenced by cytokines such as IL-6, TGF-β, IL-12, IFN-γ, IL-4, and Notch ligands.

T-Cell Effector Functions and Cytotoxicity

  • CD8 cytotoxic T-cells kill infected cells by recognizing cytosolic pathogen peptides presented on MHC I and delivering cytotoxic proteins via granules (perforin, granzymes).
  • Cytotoxic granules are specialized lysosome-like organelles; calcium-dependent exocytosis delivers content to the target cell.
  • Fas–FasL interactions contribute to apoptosis in targets expressing Fas.
  • TH1 and TH2 cells coordinate humoral and cellular responses via cytokines and co-stimulatory interactions with macrophages and B cells.
  • TH1 cells promote macrophage microbicidal activity and can help drive certain IgG responses (e.g., IgG1/IgG3 in humans).
  • TH2 cells support B-cell proliferation and isotype switching; they produce IL-4, IL-5, IL-9, IL-13 and express membrane CD40L to engage B cells.
  • TH17 cells recruit neutrophils through IL-17 and IL-6 signaling; TFH cells assist B cells in antibody production within follicles.
  • Treg cells use inhibitory cytokines (e.g., IL-10, TGF-β) and cell-contact mechanisms to restrain immune responses and maintain tolerance.

Macrophage Activation by TH1 Cells

  • TH1 cells activate macrophages to become more microbicidal via IFN-γ and CD40L signaling.
  • Activated macrophages upregulate CD40 and TNF receptors, secrete TNF-α, produce nitric oxide (NO) and superoxide (O2−), and increase MHC II expression and B7 costimulatory molecules.
  • This autocrine and paracrine signaling enhances antimicrobial activity and supports further T-cell activation.
  • Granuloma formation can occur when macrophages are chronically activated by intracellular pathogens; granulomas consist of a core of infected macrophages and surrounding immune cells, including T cells; may involve multinucleated giant cells and epithelioid macrophages; granulomas can occur in diseases like tuberculosis and sarcoidosis.

Lymphoid Tissue Trafficking and Adhesion Molecules

  • Naive and effector T-cells traffic through lymphoid tissues via an orderly sequence involving adhesion molecules and chemokines:
    • Rolling: L-selectin on T cells interacts with GlyCAM-1 and CD34 on high endothelial venules (HEVs).
    • Activation: chemokines (e.g., CCL21) activate receptors on T cells, increasing integrin affinity (e.g., LFA-1).
    • Firm adhesion: integrins bind ICAM-1/ICAM-2 on HEV endothelium.
    • Diapedesis: T cells transmigrate across the endothelium into the T-cell zones of lymph nodes.
  • Lymphocyte entry into lymph nodes occurs in stages regulated by adhesion molecules and chemokines; HEVs guide naive T-cell homing via L-selectin and chemokine receptors (e.g., CCR7 for CCL21).
  • Lymphocyte egress and recirculation resume after antigen encounter and clonal expansion.

Antigen-Presenting Cells: Distribution and Maturation

  • DCs are widely distributed in the lymph node cortex and T-cell areas; mature DCs are powerful activators of naive T cells.
  • Macrophages populate marginal sinuses and medullary cords; they actively phagocytose and present antigen while aiding in efferent lymph filtration.
  • B cells reside mainly in follicles; they can capture soluble antigens and present to CD4 T cells via MHC II.
  • Dendritic cells (DCs), macrophages, and B cells are the main APCs for naive T-cell activation; they differ in uptake, MHC II and co-stimulatory molecule expression, and anatomical localization.

Dendritic Cells: Conventional vs Plasmacytoid

  • Conventional DCs (cDCs): key antigen-presenting cells, potent in antigen presentation and T-cell activation; express CD11c and DC-SIGN (CD209) among others.
  • Plasmacytoid DCs (pDCs): major producers of interferons in response to viral infection; have distinct markers such as BDCA-2 (CD303).
  • DC maturation involves upregulation of MHC and co-stimulatory molecules (B7 family, CD40) and adhesion molecules (e.g., DC-SIGN).

B Cells as Antigen-Presenting Cells

  • B cells can efficiently present soluble protein antigens to CD4 T helper cells via MHC II.
  • B cells internalize antigen via surface immunoglobulin receptors (sIg/mIg) and process it for presentation on MHC II.
  • When antigen is not specifically bound by BCR, uptake is inefficient and fewer peptide fragments are presented.

Signals for Naive T-Cell Activation and Proliferation (Summary)

  • Three signals are required for optimal clonal expansion and differentiation:
    • Signal 1: TCR recognition of peptide–MHC complex.
    • Signal 2: Co-stimulatory signal from APCs (e.g., B7–CD28 interaction).
    • Signal 3: Cytokines shaping differentiation into TH1/TH2/TH17/TFH/Treg lineages.
  • The context of signals and the cytokine milieu determine the fate of the responding T cell and the subsequent adaptive immune response.

Summary: Antigen Processing, Presentation, and Immune Evasion Concepts

  • Antigen processing pathways localize-derived peptides to MHC I (cytosol) or MHC II (endocytic/vesicular compartments).
  • The genetic variability and polygeny of MHC genes enable diverse peptide presentation, but also drive pathogen evasion pressures.
  • Viral immunoevasins illustrate how pathogens can modulate antigen presentation to escape T-cell surveillance.
  • Proper MHC-peptide presentation is essential for effective T-cell–mediated immunity, antibody responses, and overall immune defense against pathogens.

Key Terms to Remember

  • Antigen, Antibody, Immunoglobulin (Ig), Fab, Fc, J chain, secretory component, hinge region, CDRs (CDR1, CDR2, CDR3), HV regions, FR regions, epitope, linear vs conformational epitope, hapten, cross-presentation, MHC, HLA, TAP, CLIP, HLA-DM, MIIC, invariant chain (Ii), peptide loading, TCR, CD4, CD8, co-receptors, TH1/TH2/TH17/TFH/Treg, CTL, perforin, granzymes, FasL, granuloma, DC, pDC, LFA-1, ICAM-1/2, CCR7, CCL21, GlyCAM-1, CD34, DC-SIGN, CD80/CD86, B7, TAPBP; polymorphism and codominance in MHC.

Notation Recap (LaTeX-friendly)

  • Antibody class statistics: MWIgG = 150 kDaMW_{IgG} \,=\, 150 \,\mathrm{kDa}, HC ≈50 kDaHC \,\approx 50 \,\mathrm{kDa}, LC ≈25 kDaLC \,\approx 25 \,\mathrm{kDa}, isotype weights and subclasses: IgG1-4, etc.
  • Peptide lengths: 8−10 aa8-10 \,\text{aa} for MHC I; ≥13 aa\geq 13 \,\text{aa} for MHC II.
  • Vesicular compartments: ER, MIIC, endosomes, lysosomes; proteasome structure size notes: proteasome is a 28-subunit cylindrical complex; PA28 activator can modulate access to the proteasome core.
  • Schematic terms: VH, VL; CH1, CH2, CH3; CDRs (CDR1–CDR3); HV loops; FR loops.