T-cell receptor V-region usage and antigen specificity. The cytochrome c model system.
Investigations of the I-Ek-restricted, cytochrome c-specific T-cell response in mice show that both T-cell receptor V alpha and V beta CDR3 residues and the use of particular V alpha s and V beta s are necessary for recognition. Data strongly suggest that specific CDR3 residues are important in contacting the peptide. Other experiments indicate that the requirement for V alpha:V beta conservation is not the result of strong TCR-->MHC interactions, as no correlation was found between V beta usage and changes in the alpha-helixes of the I-Ek molecule. It is also apparent that changes in V alpha or V beta usage could be elicited by changes in the side chain size of single amino acids of the antigenic peptides, suggesting that V alpha or V beta conservation is important for peptide recognition, either directly or indirectly. We also show that we can follow the cytochrome c response in vivo even in nontransgenic mice, solely by staining with anti-V region antibodies as well as mAbs directed at the activation markers CD44 and L-selectin.
Davis
M M
MM
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305-5402, USA.
McHeyzer-Williams
M
M
Chien
Y H
YH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta