Identification of a LFA-1 region involved in the HIV-1-induced syncytia formation through phage-display technology.
We have identified a peptide region on CD18 molecule (the beta subunit of the LFA-1 molecule) involved in syncytia formation of HIV-1-infected lymphocytes. Several phage clones mimicking an epitope of the CD18 cell-surface determinant were isolated from two 9-mer random peptide phage-displayed libraries via their binding to the CD18-specific monoclonal antibody (mAb) MHM23, which in in vitro assay inhibits syncytia formation in HIV-1-infected cells. The peptide sequences displayed on phages that blocked immunolabeling of this mAb on LFA-1-expressing cells were used to identify the epitope recognized by mAb MHM23 by sequence comparison. On the basis of this analysis, two peptides which inhibited syncytia formation in HIV-1-infected cells in vitro were synthesized, thus confirming that they mimic a CD18 domain that is involved in this phenomenon. The results here presented highlight the potential of phage-display technology for the study of biological processes at the basis of virus infection, but also suggest new approaches for the therapy of AIDS.
Poloni
F
F
Laboratory of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Puddu
P
P
Moretti
F
F
Flego
M
M
Romagnoli
G
G
Tombesi
M
M
Capone
I
I
Chersi
A
A
Felici
F
F
Cianfriglia
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001435:Bacteriophages / Q000235:genetics*; D003588:Cytopathogenic Effect, Viral; D018604:Epitope Mapping; D015497:HIV-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1