Variable region light chain genes encoding human antibodies to HIV-1

Molecular Immunology
D David, M Zouali

Abstract

In previous work, it was found that the heavy chain variable gene (VH) repertoire of human antibodies to HIV is markedly skewed and that the gp120 molecule is a ligand for VH3 gene products. Here, we have analysed the light chain (L-chain) variable region genes (VL) expressed by a panel of human monoclonal antibodies derived from an immunized volunteer, an AIDS patient and seropositive asymptomatic donors, and specific for HIV-1 p25, gp41 and gp120 proteins. We found that, in contrast to VH gene-family use, the VL repertoire does not exhibit a family-bias. We noticed however, a tendency to the use of VL genes that map to the downstream portion of the kappa locus. The VL genes expressed have mutated at lower rates than the corresponding VH genes and show no clustering of the replacement mutations in the hypervariable regions. We also found that the third hypervariable regions (CDR3) of the L-chains have undergone a marked diversification, with addition of untemplated nucleotides, frequent truncation at the 3' end of the VLs and somatic mutation. These molecular events result in a length heterogeneity of the CDR3s and an apparently positive selection of specific highly reactive amino acids. We conclude that the specificity of, at...Continue Reading

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Citations

May 1, 1996·Molecular Immunology·M Ohlin, C A Borrebaeck
Sep 29, 1999·Immunology Today·F J Stevens, Y Argon
Sep 9, 2015·The Journal of Infectious Diseases·Mohammad M SajadiGeorge K Lewis
Feb 3, 2007·Immunobiology·Mabel RodríguezAna María Vázquez
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Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·David H MargolinNorman L Letvin

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