2.1 T lymphocyte development

T cells recognize what in MHC?

peptide; MHC most diverse set of genes

ineracts w MHC + peptide

how are TCRs made?

randomly through V(D)J recombo

how do we end up w TCR that see target peptide in MHC?

what prevents our T cels from targeting self peptides

explain the difference between T and B cell receptor structure

is there a soluble form of TCR?

no! so there is no CSR and SH

what are the two chains of the TCR?

alpha and beta

few have gamma and delta

what is always associated wth TCR?

CD3; it transduces signals this way (vs CD19 and CD 20 for B cell)

which cell receptor

• recognizes antigen but does not have intracellular tails

• CD3 makes it invariant

TCR

what antigen type do TCR recognize?

protein antigen, not soluble

how do pathogens and protein antigens get into host cell?

infection or ingestion by endocytosis or phagocytosis (know MHC class I vs class II, APC vs self peptides)

how many alleles possible?

12! (see 1.3)

THC restriction, interacts with only 1 allele w/in said sid

MHC restriction

mature αβ T cells recognize peptides of antigenic proteins that are bound to MHC as peptide–MHC (pMHC) complexes, but essentially nothing else

MHC Class I on expressed on

ALL nucleated cells (not RBCs and platelet)

MHC class II expressed on

APCs: DC, B cell, macrophages (phagocytic)

thymic non-lymphoid cells

CD4 positive T cells recognize the peptides

CD8 and CD4 are (BLANK) that (BLANK) binding and (BLANK) signaling

co-receptors

stabilize

enhance

*do not bind antigen but bind to constant part of MHC

explain in short plain terms T cell, alpha beta, and co-receptor

TCR: V(D)J but no SH and CSR; CD3 signal transduction

chains, antigen recognition

co-receptor determines function

what are the 3 key molecules expressed by T cells?

• TCR: alpha and beta chains for antigen recognition

• CD3: signal transduction w TCR

• co-receptors: CD4 and CD8 adhesion and enhanced signal transduction through TCR

what are the differences in chains btwn TCR and BCR?

TCR: two chains alpha and beta

BCR: four chains 2H and 2 L

what are the differences in antigen binding sites btwn TCR and BCR?

TCR: one

BCR: two

what are the differences in recognition of antigen types btwn TCR and BCR?

TCR: protein, peptides

BCR: protein, carbs, lipids

what are the differences in Ag bound/solubility btwn TCR and BCR?

TCR: Ag bound by MHC

BCR: Ag can be free/soluble

what are the differences in secretion btwn TCR and BCR?

TCR: not secreted

BCR: secreted as Ab by plasma cell

what are the differences in SHM btwn TCR and BCR?

TCR: no

BCR: yes

what are the differences in CSR btwn TCR and BCR?

TCR: not needed, CD3 invariant

BCR: IgG, IgA, IgE

what is primary lymphoid organ for T cell development?

thymus

explain DiGeorge Syndrome

• little or no thymus

• affects heart and parathyroid

• characteristic facial features

• no mature T cells and recurrent infections

no thymus = no mature T cells

explain thymocyte to mature T cell

thymocyte migrate through thymus V(D)J recombo and eventually we get mature CD4 and CD8 positive T cells

what could lead to T cells dying?

no working receptor

does not work with MHC

explain early stages of T cell diff in thymus: rhomboid slide

• double negative: no CD4 or CD8

• double positive: CD4 and CD8 (only in T cell development in thymus, double pos in thymocyte in periphery? cancer)

• selection: “T cell edu” test with MHC

  • bind class 1: CD8

  • bind class II: CD4

what do double positive thymocytes interact with?

cortical epithelial cells which have class I and II on surface

interaction = survival

detailed positive selection

• DP cells with both CD4 and CD8 receptors

• thymic epithelial cells with MHC Class I and II molecules

• binds to said class? lineage commit

  • stop making unneeded co-receptor

• CD4 class II CD8 Class I

what would happen if there was a lack of positive selection?

double positive, recognize both = death, no T cells

what would the T cells look like of an animal with no MHC Class II?

no CD4

explain negative selection

for cells that recognize self, go to medulla, they are single positive and if they interact with self peptide with thymic dendritic cell they die

thymus transcribe proteins that would be produced in tissues all over the body; good filter!

simple negative selection

interaction = death

what would happen if there was a defect in negative selection?

self reactive T cells; autoimmune

main summary of T cell differentiation:

naive T cells from thymus

• respond to foreign antigen bound in host MHC (HLA)

  • evert T cell works with one HLA!

• do not respond to self aka tolerant to self