T lymphocytes recognize short peptide fragments of proteins bound to major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. There are two classes of MHC molecules - MHC class I presents peptides to CD8+ T cells on all nucleated cells, while MHC class II presents peptides to CD4+ T cells on professional antigen-presenting cells. Peptides bind to MHC molecules through anchor residues in a specific sequence motif, and a single MHC molecule can bind many different peptides. MHC molecules are highly polymorphic, which limits T cell recognition to peptides bound to self MHC molecules only.

1. Antigen Recognition by
T Lymphocytes

3. Antigen Presenting Cell

4. T Cell-Antigen Recognition
• Respond to contiguous short amino acid
sequences in proteins-T Cell Epitopes
– Peptides
– Not Native Protein
• T cells do not bind free peptides
• T Cells Recognize a complex of a peptide
fragment bound to the membrane
proteins of cells- Major
histocompatibility complex (MHC)
molecules

6. MHC Molecules
• MHC I
• MHC II
• Physiological function is to present
peptides to T cells

7. Major Histocompatibility Complex
Proteins
• Human-HLA (human leukocyte
antigen)
• Mouse: H-2
• Bovines: BoLA
• Equines: ELA
• Swine: SLA
• OLA, CLA, DLA, FLA

9. MHC Class I Molecules

10. MHC Class I Molecules
• Present Peptides to CD8+ T Cells
• Expressed on ALL Nucleated Cells
of the Body

13. Recognition of
Peptide/MHC I Complex
By the T Cell Antigen
Receptor

15. MHC Class II Molecules

16. MHC Class II Molecules
• Present Peptides to CD4+ T Cells
• Expressed on Dendritic Cells, B
Cells, Macrophages-Professional
Antigen Presenting Cells

18. Crystal Structure of MHC
Class II Molecules
Peptide

21. General Characteristic of Peptide-
MHC Interactions
• Each MHC class I & class II
molecule has a single peptide
binding cleft that can bind many
different peptides
• Anchor Residues

22. Peptide Binding to MHC Molecules
via Anchor Residues

23. • Two different
Peptides bind the
same MHC
• Sequence Motif

24. Features of Peptide Binding to MHC Molecules

25. Features of Peptide Binding to MHC Molecules

26. MHC Polymorphism

29. Properties of MHC Molecules and Genes

30. Limited Polymorphism in the MHC Genes causes?

31. Self MHC Restriction

32. Both CD4+ and CD8+ T cells
can recognize antigen only when
presented by a self-MHC
molecule on the membrane of an
antigen presenting cells
CD4+ T Cells-Self MHC II-
Restricted
CD8+ T Cells-Self MHC I-
Restricted
Self MHC Restriction

34. (non-self MHC)

35. Antigen
BCR
B Cell
B Cell Antigen
Recognition
T Cell
APC
T Cell Antigen
Recognition
TCR
MHC+Peptide

36. T Cell Subsets
T
Helper
Cell
TCR
CD3CD4
T
Cytotoxic
Cell
TCR
CD3CD8
MHC Class II MHC Class I
+ Peptide + Peptide
Recognizes