title: Human T cell repertoire generation in the absence of MHC class II expression results in a circulating CD4+CD8- population with altered physicochemical properties of complementarity-determining region 3.
abstract: In this study, we have investigated the impact of deficient MHC class II expression on the use of TCRBV6 and TCRBJ gene elements, and on the pattern of amino acid incorporation exhibited in the N1-D-N2 segments of the third complementarity-determining region (CDR3) of these TCRBV6 rearrangements. To this end, we have analyzed circulating T cells from three, nonrelated MHC class II-deficient (bare lymphocyte syndrome (BLS)) patients and three MHC class II-expressing family members. The patients and healthy controls exhibited similar, nonrandom usage profiles of TCRBV6 and TCRBJ gene elements in both the CD4+CD8- and the CD4-CD8+ subsets of peripheral blood T cells. No statistically significant differences between patients and controls were detected in the length of CDR3, or in the amount of non-germline modification at the sites of recombination. However, detailed analysis of the TCRBV6 rearrangements derived from the CD4+CD8- subsets from the BLS patients revealed patterns of amino acid incorporation into the N1-D-N2 region of CDR3 that resulted in altered charge and hydropathicity properties of the presumed Ag binding site. In this way, we have been able to demonstrate that human T cell repertoire development in the absence of MHC class II expression results in a circulating CD4+CD8- T cell population bearing TCRs with altered CDR3 profiles. Such altered profiles are likely to be a direct reflection of the lack of MHC class II-mediated selection processes in these BLS patients.
authors.affiliation: Department of Immunohematology, University Hospital Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Henwood
authors.forename: M C
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: A H
authors.initials: AH
authors.lastname: van Boxel-Dezaire
authors.forename: R
authors.initials: R
authors.lastname: Schipper
authors.forename: M
authors.initials: M
authors.lastname: den Hoedt
authors.forename: A
authors.initials: A
authors.lastname: Peijnenburg
authors.forename: O
authors.initials: O
authors.lastname: Sanal
authors.forename: F
authors.initials: F
authors.lastname: Ersoy
authors.forename: G T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: B J
authors.initials: BJ
authors.lastname: Zegers
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
authors.forename: M J
authors.initials: MJ
authors.lastname: van Tol
authors.forename: P J
authors.initials: PJ
authors.lastname: van den Elsen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens; D016827:CD8 Antigens; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D007526:Isoelectric Point; D008969:Molecular Sequence Data; D005810:Multigene Family; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000737:chemistry* / Q000145:classification / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006681:HLA-D Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta