T cell and HLA molecules

What are Major Histocompatibility Complex (MHC) molecules?

cell-surface glycoproteins

present peptide antigens to T- cells

essential for self and non self recognition

required for T-cell activation

Where are MHC genes located?

• Located on chromosome 6

• Called HLA (Human Leukocyte Antigen) genes

Large gene cluster (>200 genes)

What is the basic structure of MHC molecules?

• Composed of two polypeptide chains

• Forms a peptide-binding groove

Groove determines peptide specificity

Where is MHC Class I expressed?

• On all nucleated cells

Not expressed on red blood cells

What is the structure of MHC Class I?

• α heavy chain + β₂-microglobulin

• Peptide-binding groove formed by α1 and α2 domains

• Groove is closed at both ends

• Binds 8–10 amino acid peptides

What is the function of MHC Class I?

• Presents intracellular (endogenous) antigens

• Recognised by CD8⁺ cytotoxic T cells

• Important for killing virus-infected and tumour cells

How are antigens processed for MHC Class I?

• Cytosolic proteins degraded by proteasomes

• Peptides transported into ER via TAP proteins

• Loaded onto MHC I → transported to cell surface

Where is MHC Class II expressed?

• Only on antigen-presenting cells (APCs)

• Dendritic cells

• Macrophages

• B lymphocytes

What is the structure of MHC Class II?

• α chain + β chain

• Peptide-binding groove is open at both ends

Binds longer peptides (13–25 amino acids)

What is the function of MHC Class II?

• Presents extracellular (exogenous) antigens

• Recognised by CD4⁺ helper T cells

• Activates adaptive immune responses via cytokines

How are antigens processed for MHC Class II?

• Antigens taken up by endocytosis/phagocytosis

• Degraded in lysosomes

• Invariant chain (Ii) prevents early binding

• HLA-DM removes CLIP → peptide loaded

What antigens do Class I and Class II MHC present?

• Class I: intracellular antigens

• Class II: extracellular antigens

Which T cells recognise MHC Class I and II?

• Class I → CD8⁺ cytotoxic T cells

• Class II → CD4⁺ helper T cells

How does peptide length differ between Class I and II?

• Class I: 8–10 amino acids

• Class II: 13–25 amino acids

What does MHC polymorphism mean?

• Many allelic variants of each MHC gene

• Individuals usually heterozygous

• Major barrier to organ transplantation

What does MHC polygeny mean?

• Multiple different MHC genes expressed per individual

• Several Class I and Class II molecules at once

Why are MHC polymorphism and polygeny important for immunity?

• Increase range of peptides presented

• Prevent pathogen immune escape

• Improve population-level survival