Tax and M1 peptide/HLA-A2-specific Fabs and T cell receptors recognize nonidentical structural features on peptide/HLA-A2 complexes.
Both TCRs and Ab molecules are capable of MHC-restricted recognition of peptide/MHC complexes. However, such MHC restriction is the predominant mode of recognition by T cells, but is extremely rare for B cells. The present study asks whether the dichotomy in Ag recognition modes of T and B cells could be due to fundamental differences in the methods by which TCRs and Abs recognize peptide/MHC complexes. We have compared MHC and peptide recognition by panels of CTL lines specific for the Tax and M1 peptides presented by HLA-A2 plus Tax and M1 peptide/HLA-A2-specific human Fabs that were selected from a naive phage display library. Collectively, the results indicate both striking similarities and important differences between Fab and TCR recognition of MHC and peptide components of the Tax and M1/HLA-A2 complexes. These findings suggest that these two classes of immunoreceptors have solved the problem of specific recognition of peptide/MHC complexes by nonidentical mechanisms. This conclusion is important in part because it indicates that Ab engineering approaches could produce second-generation Ab molecules that more closely mimic TCR fine specificity. Such efforts may produce more efficacious diagnostic and therapeutic agents.
Biddison
William E
WE
Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. web@ninds.nih.gov
Turner
Richard V
RV
Gagnon
Susan J
SJ
Lev
Avital
A
Cohen
Cyril J
CJ
Reiter
Yoram
Y
D019943:Amino Acid Substitution / Q000235:genetics / Q000276:immunology; D000918:Antibody Specificity; D017951:Antigen Presentation; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D016356:Gene Products, tax / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D008024:Ligands; D046911:Macromolecular Substances; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; D015789:HLA-A2 Antigen; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014763:Viral Matrix Proteins