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 partial homology with human leukocyte antigen (HLA) class I or class II. One functional similarity is the ability of gp120 and HLA class II to bind CD4. Given the close association between HIV-induced disease and the amount of immune activation and anergy, features closely associated with chronic allogenic stimulation, we asked whether gp120 shared any other properties of HLA, in this case the ability to bind peptides.


METHODS
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-polyacrylamide gel electrophoresis.


RESULTS
A signal peptide binding to HLA class I and a haemagglutinin peptide that binds to HLA class II were found to bind soluble gp120 specifically; binding and cross-linking could be competed out with excess of the unmodified peptides but not unrelated control peptides. Molecular modelling of gp120 suggests shared anchor sites for peptides binding to both HLA and gp120 soluble molecules.


CONCLUSIONS
The ability to bind these two peptides suggests that gp120 has a peptide-binding site of broad specificity, which if functional in vivo, could compete with normal peptide loading of major histocompatibility complex (MHC) class I and/or class II peptides, as well as aberrantly stimulate the T-cell receptor (by virtue of its potential to be mistaken for an allogenic MHC/peptide complex), resulting in immune activation, anergy and apoptosis in susceptible hosts.
Sheikh
M J
MJ
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London, UK.
Ongrádi
J
J
Austen
B M
BM
Dalgleish
A G
AG
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D000939:Epitopes / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006680:HLA Antigens; D010455:Peptides