Peptide specificity of alloreactive CD4 positive T lymphocytes directed against a major histocompatibility complex class I disparity.
The mouse strains C57BL/6 (B6, H2b) and Kbm1 mutant bm1 have a defined difference of three amino acids at position 152, 155, and 156 in the MHC class I K molecule. This causes a change in the side and the bottom of the antigen presenting groove of the K molecule resulting in strong allogeneic responses in vitro and in vivo. Here we report on the peptide specificity of CD4+ T cells of B6 origin directed against the Kbm1 mutant and speculate on the peptide specificity of CD8+ bm1-specific T lymphocytes of B6 origin. Bm1-specific CD4+ T helper cells recognized a peptide derived from the Kbm1 molecule encompassing the three mutations, presented by MHC class II molecules on syngeneic cells. The ability of this peptide to bind to MHC class II resulted from amino acid mutations at positions 155 and 156. Furthermore, the recognition of the natural peptide derived from the Kbm1 molecule presented by MHC class II I-Ab molecules on cells of bml origin could be blocked by addition of an MHC class II I-Ab binding competitor peptide. Thus, due to the mutations in an MHC class I molecule, indirect presentation via MHC class II molecules and MHC class II-restricted recognition of a peptide derived from such a MHC class I molecule is demonstrable.
Ossevoort
M A
MA
Department of Immunohematology and Blood Bank, University of Leiden, The Netherlands.
De Bruijn
M L
ML
Van Veen
K J
KJ
Kast
W M
WM
Melief
C J
CJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010455:Peptides / Q000276:immunology
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D010455:Peptides