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MHC = HLA

• Major Histocompatibility Complex (MHC) is rephrased as Human Leukocyte Antigen (HLA)
• Genetic loci are on 6th chromosome

MHC and T cell receptor (TCR)

• MHC presents peptide antigen and TCR recognize it
• CD8 acts as co-receptor to MHC Class I on all target cells
• CD4 acts as co-receptor to MHC Class II on antigen-presenting cells

class	genetic loci	expression	domains	TCR on T cell	binding cleft
MHC Class I	HLA-A HLA-B HLA-C	all nucleated cells	α1, α2 ――― β2MG, α3	TCR+CD8 on target cells CD8 binds to α3	peptide with 8-9 AAs
MHC Class II	HLA-DP HLA-DQ HLA-DR	dendritic cell macrophage B cell activated T cell some epitherial cells in thymus and intestine	α1, β1 ――― α2, β2	TCR+CD4 on antigen presenting cell CD4 binds to β2	peptide with 18-20 AAs
MHC Class III

T cell development

1. Prothymocytes migrate from bone marrow to thymus
2. Prothymocytes proliferate and become Thymocytes in thymus
3. Thymocytes express all of CD3, CD4 and CD8 (Double positive thymocytes)
4. DP thymocytes are challenged to bind peptide-MHC (Positive selection)
5. CD8+ thymocytes are to suppress CD4 expression, vise versa (Single positive CD8 or CD4 cells)
6. SP cells encounter Epitherial reticular cells (APC - DC, Macrophage) and challenged to bind too efficiently to pMHC I or pMHC II (Negative selection)
7. SP cells which do not bind too efficiently to pMHC I or pMHC II exit thymus as (naive) T cells

T cell activation by 2 signaling (2 signal model)

• Naive T cell needs doubled signals of TCR-pMHC interaction and co-stimulatory molecules by APC to be activated
• Co-stimulatory molecules: CD28, ICOS, CTLA-4 and PD-1

1. CD28 and ICOS on T cell acts as activation signal
2. CTLA-4 and PD-1 on T cell acts as inhibitory signal against activation

CD8+ T cell functions

• Cytotoxicity
  • Killing virus-infected cells, malignant cells

1. Perforin/granzyme-mediated
2. Fas/Fas ligand-mediated

• IFN-γ production

CD4+ T cell differentiation

*Tfh = follicular B helper T cell