Immunogenetics

Thompson, A.; Brouns, Gaby S.; Schuurman, Ruud K. B.; Borst, Jannie; Timmers, Erik

doi: 10.1007/s002510050437pmid: 9745007

 B-cell commitment is characterized by the expression of specific membrane proteins and the rearrangement and expression of immunoglobulin (Ig) heavy (H) and light (L) chain genes. At early stages of B-cell development, unrearranged Ig loci are transcribed, which correlates with these regions becoming accessible for Ig gene rearrangement. Some germline transcripts can be translated into protein and potentially play a role in cell signaling during B-cell development. In this report an early stage in human B-cell development is characterized using Epstein-Barr virus (EBV)-transformed cell lines from patients with a severe combined immunodeficiency (SCID). These lines were shown to produce germline constant (C) gene transcripts from the IGH and IGK loci. We demonstrate here that these cells are committed to the B-cell lineage as substantiated by expression of CD79a and CD79b. No surrogate light chain (SLC) gene transcription was detected, indicative of a very early differentiation stage. From these cell lines two types of germline IgV gene transcripts were isolated: a transcript containing the IGKV4-1 gene and a germline IGHV-1 transcript nearly identical to IGHV1/OR15-1 (HC15-1, DP-1), an orphon V H gene on chromosome 15. Germline V H transcripts originating from the V H locus on chromosome 14 could not be detected. It is of interest that, apart from Ig V and C genes (non-functional), V genes that reside outside the Ig locus are a target for the transcription factors that are postulated to initiate Ig gene rearrangement early in B-cell development.

Jakobsen, I. B.; Wilson, Susan R.; Easteal, S.

doi: 10.1007/s002510050438pmid: 9745008

 Some alleles of the major histocompatibility complex (MHC) genes have a reticulate pattern of evolution, probably resulting from the exchange of segments by gene conversion or recombination. Here we compare the extent and patterns of reticulate evolution among the classical class I and class II loci of the human MHC using the recently developed compatibility and partition matrix methods. A complex pattern is revealed with substantial differences among loci in the extent and pattern of reticulation. Extremely high levels of reticulation are observed at HLA-B and HLA-DPB1, high levels at HLA-A and HLA-DRB1, moderate levels at HLA-C and HLA-DQB1, and low levels at HLA-DQA1. The reticulate events are concentrated in the exons encoding the highly variable, peptide-binding domains, suggesting that the sequence combinations produced by these events are maintained by natural selection.

Cano, P.; Fan, B.; Stass, Sanford

doi: 10.1007/s002510050439pmid: 9745009

 HLA class I alleles are studied by representing them in a metric space where each dimension corresponds to each one of the amino acid positions. Their similarity in reference to their ability to present peptides to T cells is then evaluated by calculating the correlation matrix between the amino-acid-composition tables (or binding affinity tables) for the sets of peptides presented by each allele. This correlation matrix is considered an empirical similarity matrix between HLA alleles, and is modeled in terms of possible structures defined in the metric space of HLA class I amino acid sequences. These geometric structures are adequate models of the peptide-binding data currently available. The following clusters of HLA class I molecules are identified in reference to their ability to present peptides: Cluster I) HLA-A3/ HLA-A11/ HLA-A31/ HLA-A33/ HLA-A68; Cluster II) HLA-B35/ HLA-B51/ HLA-B53/ HLA-B54/ HLA-B7; and Cluster III) HLA-A29/ HLA-B61/HLA-B44; the last cluster showing possible similarities between alleles from different loci. In modeling these natural clusters, the geometric structures with more predictive power confirm the importance of those positions in the peptide-binding groove, particularly those in the B pocket. In addition, other positions (46, 79, 113, 131, 144, and 177) appeared to bear some relevance in determining which peptides can be presented by which HLA alleles.

Kawahito, Y.; Remmers, Elaine F.; Wilder, R. L.; Longman, Ryan E.; Gulko, Pércio S.; Wang, Jianping; Chen, Stephen; Chang, Lisa; Reese, V. R.; Dracheva, Svetlana; Ge, Lynn; Hoffman, Jean H.; Shepard, Jennifer; Cannon, Grant W.; Griffiths, Marie M.

Criscitiello, Michael F.; Benedetto, Ralph; Antao, Aurita; Wilson, Melanie R.; Chinchar, V. Gregory; Miller, Norman W.; Clem, L. William; McConnell, T. J.

doi: 10.1007/s002510050441pmid: 9745011

Vestberg, M.; Brunsberg, Ulrica; Bergsteinsdottir, Kristin; Karlsson, Mikael; Gustafsson, Kenth; Wedekind, Dirk; Hedrich, Hans; Holmdahl, Rikard

doi: 10.1007/s002510050442pmid: 9745012

Dumrese, Tilman; Stevanović, Stefan; Seeger, Florian H.; Yamada, N.; Ishikawa, Yoshihide; Tokunaga, Katsushi; Takiguchi, M.; Rammensee, H.-G.

doi: 10.1007/s002510050443pmid: 9745013

O'Rourke, A. M.; Escuro, Guia; Feeney, Ann J.

doi: 10.1007/s002510050444pmid: 9745014

Sillibourne, James E.; Kay, R. A.

doi: 10.1007/s002510050445pmid: 9745015

White, G. P.; Roche, Peter; Brandon, Malcolm R.; Newton, Susan E.; Meeusen, Els N. T.

doi: 10.1007/s002510050446pmid: 9745016