MHC class II peptide flanking residues of exogenous antigens influence recognition by autoreactive T cells.
Molecular mimicry between exogenous microbial antigens and self-epitopes has been proposed as a triggering mechanism for autoimmune diseases for many years. We reported that a peptide from a protein specific to Chlamydia pneumoniae (Cpn0483) which shares a motif with the dominant encephalitogenic epitope of the self-antigen, rat myelin basic protein (rat68-86), elicits experimental autoimmune encephalomyelitis (EAE) in Lewis rats. We recently observed that rat68-86 utilizes aspartic acid (D) and arginine (R) in the common motif as primary and secondary TCR contacts, respectively. In contrast, the encephalitogenic activity of Cpn0483 is dependent on R and the C-terminal asparagine (N), which flanks the MHC class II-P9 anchor residue. Thus, rat68-86 and Cpn0483 share a common motif, are encephalitogenic and are both restricted by MHC class II RT1.B(l). T cells from rats immunized with the encephalitogenic Cpn0483 peptide proliferated to the priming peptide as well as to the non-encephalitogenic CpnN>A analog. However, CpnN>A-primed T cells did not respond to the native Cpn0483 peptide. We conclude that the MHC-flanking C-terminal asparagine residue markedly influences T cell recognition by the chlamydial peptide.
Conant
Stephanie B
SB
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Swanborg
Robert H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001216:Asparagine; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C079716:myelin basic protein 68-88; D001216:Asparagine