NDLI: Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response.

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Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response.

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Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Burstyn, D. Zauderer, M. Natarajan, K.
Description	Author Affiliation: Natarajan K ( Cancer Center, University of Rochester School of Medicine, NY 14642.);
Abstract	Dominant expression of T-cell receptor (TCR) alpha or beta chain variable region (V alpha or V beta) gene families has been observed in the T-cell response to some conventional peptide antigens. Current models for the interaction of TCR V region elements with different determinants of a major histocompatibility complex (MHC)-peptide complex, the normal TCR ligand, suggest that the TCR V-J junctional region (CDR3, where J is joining) is the primary contact with a peptide epitope and that other TCR V region segments may interact directly with neighboring MHC determinants. This suggests that V alpha or V beta dominance in a specific response can be MHC-selected. In this case, if related peptides bind to an MHC molecule in a similar orientation, they could select for identical V alpha or V beta dominance even if they are noncrossreactive at the level of T-cell activation. We have screened for this possibility by introducing minimal conservative substitutions in a synthetic peptide, YYEELLKYYEELLK, that is presented to T cells in association with an uncommon A beta E alpha d mixed Ia isotype. We report here that the peptide variant FFEELLKFFEELLK is noncrossreactive with YYEELLKYYEELLK but appears to preserve the same MHC binding motif since T-cell responses are restricted to the same mixed A beta E alpha isotype. Although the two peptides are noncrossreactive in either direction, the same members of the V alpha 4 gene family are dominantly expressed in T cells specific for either peptide. We conclude that the similar topography of the two MHC-peptide complexes gives functional significance to a unique A beta E alpha determinant that selects for V alpha 4 dominance.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Major Histocompatibility Complex Receptors, Antigen, T-Cell Genetics T-Lymphocytes Immunology Amino Acid Sequence Animals Antibodies Antigen-Presenting Cells Cloning, Molecular Cross Reactions DNA Gene Library Haplotypes L Cells (Cell Line) Lymphocyte Activation Macromolecular Substances Mice Mice, Inbred BALB C Mice, Inbred C3H Molecular Sequence Data Oligodeoxyribonucleotides Peptides Chemical Synthesis Poly A Isolation & Purification Polymerase Chain Reaction RNA RNA, Messenger Transfection Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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