THE GP120 ENVELOPE OF HIV-1 BINDS PEPTIDES IN A SIMILAR MANNER TO HUMAN-LEUKOCYTE ANTIGENS

Objective: All the conserved regions of HIV gp120 have at least some p artial homology with human leukocyte antigen (HLA) class I or class II . One functional similarity is the ability of gp120 and HLA class II t o bind CD4. Given the close association between HIV-induced disease an d the amount of immune activation and anergy, features closely associa ted with chronic allogenic stimulation, we asked whether gp120 shared any other properties of HLA, in this case the ability to bind peptides . Design: T-cell epitope peptides known to bind to soluble HLA class I or class II were photolabelled and made radioactive. Cross-linking of modified peptides to soluble HLA class I, II and gp120 was activated by ultraviolet light and analysed by sodium dodecylsulphate-polyacryla mide gel electrophoresis. Results: A signal peptide binding to HLA cla ss I and a haemagglutinin peptide that binds to HLA class II were foun d to bind soluble gp120 specifically; binding and cross-linking could be competed out with excess of the unmodified peptides but not unrelat ed control peptides. Molecular modelling of gp120 suggests shared anch or sites for peptides binding to both HLA and gp120 soluble molecules. Conclusions: The ability to bind these two peptides suggests that gp1 20 has a peptide-binding site of broad specificity, which if functiona l in vivo, could compete with normal peptide loading of major histocom patibility complex (MHC) class I and/or class II peptides, as well as aberrantly stimulate the T-cell receptor (by virtue of its potential t o be mistaken for an allogenic MHC/peptide complex), resulting in immu ne activation, anergy and apoptosis in susceptible hosts.