The MHC class II-restricted T cell response of C57BL/6 mice to human C-reactive protein: homology to self and the selection of T cell epitopes and T cell receptors.
The T cell response of C57BL/6 mice to human C-reactive protein (hCRP), an inducible acute phase protein, was analysed. Two I-A(b)-restricted epitopes at positions 79 95 (epitope A) and 87-102 (epitope B) were identified using a panel of CD4+ T cell clones. Human C-reactive protein shares considerable homology with mouse C-reactive protein and mouse serum amyloid P component. Interestingly, the two epitopes map to the region of lowest homology between human CRP and its mouse homologues. Human CRP-specific T cell clones express a restricted T cell receptor (TCR) repertoire, both with regard to usage of TCR germline gene segments (V alpha, J alpha, V beta, J beta) and certain TCR alpha beta combinations. Therefore, epitope-A specific clones preferentially use TCR V beta8.3 and V alpha3 J alpha15 V beta8.3-J beta2.3 and epitope-B specific clones use V beta2 and V alpha1-J alpha24/30-V beta2. This bias is even more pronounced when TCR usage is correlated with epitope fine specificity. A role for homology of hCRP to self components in selecting these particular T cell epitopes and TCR is discussed.
Döffinger
R
R
Tumor Immunology Programme, Division of Cellular Immunology, German Cancer Research Centre, Heidelberg, Germany.
Klein
T C
TC
Pepys
M B
MB
Casanova
J L
JL
Kyewski
B A
BA
D000595:Amino Acid Sequence; D000818:Animals; D002097:C-Reactive Protein / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D017634:Self Tolerance; D016415:Sequence Alignment; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D002097:C-Reactive Protein