Document 0999
 DOCN  M9540999
 TI    Influence of human leukocyte antigen genes on TCR V gene segment
       frequencies.
 DT    9504
 AU    Genevee C; Farace F; Chung V; Diu A; Raffoux C; Charron D; Hercend T;
       Triebel F; Laboratoire d'Immunologie Cellulaire, INSERM U 333, Institut;
       Gustave Roussy, Villejuif, France.
 SO    Int Immunol. 1994 Oct;6(10):1497-504. Unique Identifier : AIDSLINE
       MED/95127552
 AB    Human leukocyte antigen (HLA)-dependent selection mechanisms exerted
       during thymic maturation are supposed to be main contributing factors to
       the genetic predetermination of the TCR repertoire and may have a
       detectable effect on adult peripheral blood lymphocyte V segment
       frequencies. Here, we analyzed whether polymorphic or non-polymorphic
       HLA determinants are associated with selected expression of some V gene
       segment specificities. We first examined the reactivity of 17 V segment
       specific mAb on purified CD4+ and CD8+ cell fractions in 10 unrelated
       people. We found a significant overexpression of only three V segment
       products (V beta 2, V beta 5.1 and V beta 6.7) in CD4+ and none in CD8+
       cell fractions in most individuals. Skewing of certain V beta segments
       by non-polymorphic HLA determinants (i.e. class II for CD4+ and class I
       for CD8+ cells) is therefore more limited (3/17) than previously
       thought. Considering the effects of polymorphic HLA determinants, we
       compared TCR V segment frequencies in HLA-identical siblings to sibling
       pairs who differ at one or both HLA haplotypes, using 13 V beta specific
       mAb. In pairwise comparisons, we found that the HLA complex had no
       detectable effect on TCR repertoire in five large families with multiple
       siblings. Together, these observations suggest that HLA-predicted
       selection mechanisms exerted during thymic maturation might not have a
       predominant influence shaping the TCR repertoire of normal adults.
 DE    Antibodies, Monoclonal/IMMUNOLOGY  CD4-Positive T-Lymphocytes/IMMUNOLOGY
       CD8-Positive T-Lymphocytes/IMMUNOLOGY  Flow Cytometry  Gene Frequency
       Haplotypes/*GENETICS  Human  HLA
       Antigens/BIOSYNTHESIS/*GENETICS/IMMUNOLOGY  Polymerase Chain Reaction
       Receptors, Antigen, T-Cell, alpha-beta/BIOSYNTHESIS/*GENETICS/
       IMMUNOLOGY  JOURNAL ARTICLE

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