Document 0192
 DOCN  M9650192
 TI    Analysis of major histocompatibility complex class I-restricted hapten
       recognition by mutation of the V-J joining of T cell receptor alpha
       chains.
 DT    9605
 AU    von Bonin A; Plaga S; Ruh H; Hebbelmann S; Pflugfelder U; Martin S;
       Weltzien HU; Max-Planck-Institut fur Immunbiologie, Freiburg, Germany.
 SO    Eur J Immunol. 1996 Jan;26(1):179-86. Unique Identifier : AIDSLINE
       MED/96152743
 AB    Hapten-specific T cell responses are responsible for chemically induced
       immune disorders. However, the molecular details of hapten interactions
       with T cell receptors (TCR) are poorly understood. Recent studies of
       trinitrophenyl (TNP)-specific responses revealed major
       histocompatibility complex-associated TNP-peptides as dominant epitopes
       for CD8+ and CD4+ T cells. The present study is based on the observation
       that two H-2Kb/TNP-specific CTL clones (II/7 and III/1), differing
       exclusively in two amino acids of their TCR alpha chains, also differed
       in their carrier specificities for various TNP-peptides. The genes of
       the two alpha chains and the common beta chain were cloned into
       expression vectors. Transfection of the TCR alpha chain of clone III/1
       into a hybridoma of clone II/7 also transferred the fine specificity of
       clone III/1, indicating that the small alpha chain variations were
       indeed responsible for the different carrier specificities. Point
       mutations bridging the difference between the alpha chains of clones
       II/7 and III/1 and functional studies of the respective TCR alpha beta
       transfectants into a TCR-negative hybridoma revealed an unexpected
       result: the two receptors did not represent examples of structural
       complementarity for different sets of hapten-peptide conjugates; rather,
       they resembled two structures of principally similar specificity but of
       significantly different overall affinity. This was demonstrated more
       directly by comparing the fine specificities of III/1 transfectants
       expressing or not expressing the co-receptor CD8: the CD8-negative III/1
       transfectant assumed a specificity pattern indistinguishable from that
       of a CD8-expressing, II/7-derived transfectant. Hence, comparable
       alterations of antigen recognition may be induced either by subtle TCR
       alterations or by removal of CD8, i.e. by the presence or absence of a
       non-polymorphic adhesion molecule.
 DE    Amino Acid Sequence  Animal  Antigen Presentation/GENETICS  Base
       Sequence  CD8-Positive T-Lymphocytes/PHYSIOLOGY  Epitopes/GENETICS  H-2
       Antigens/*GENETICS/IMMUNOLOGY  Haptens/*GENETICS/IMMUNOLOGY  Hybridomas
       Mice  Molecular Sequence Data  Mutagenesis, Site-Directed/*IMMUNOLOGY
       Receptors, Antigen, T-Cell, alpha-beta/*GENETICS/IMMUNOLOGY  Support,
       Non-U.S. Gov't  T-Lymphocytes, Cytotoxic/IMMUNOLOGY
       Transfection/IMMUNOLOGY  JOURNAL ARTICLE

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