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

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In previous work, it was found that the heavy chain variable gene (V H) repertoire of human antibodies to HIV is markedly skewed and that the gp120 molecule is a ligand for V H3 gene products. Here, we have analysed the light chain (L-chain) variable region genes (V L) 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 V H gene-family use, the V L repertoire does not exhibit a family-bias. We noticed however, a tendency to the use of V L genes that map to the downstream portion of the kappa locus. The V L genes expressed have mutated at lower rates than the corresponding V H 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 V Ls and apparantly positive selection of specific highly reactive amino acids. We conclude that the specificity of, at least some of the anti-HIV antibodies, is dictated by the L-chain CDR3 regions which bear the imprints of antigenic selection.