Reciprocal recognition of an HLA-Cw4-restricted HIV-1 gp120 epitope by CD8+ T cells and NK cells.
OBJECTIVE
The HIV-1 Nef protein selectively downregulates human leukocyte antigen (HLA)-A and HLA-B but not HLA-C molecules on the surface of infected cells. This allows HIV-infected cells to evade recognition by most cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. We investigated the recognition of an HLA-Cw4-restricted HIV-1 gp120 epitope SFNCGGEFF (SF9) and its variant SFNCGGEFL (SL9) by T cells and NK receptors.


METHODS
Recognition of HIV-1 gp120 peptides (SF9 and SL9) by T-cell clones was measured by staining with HLA-Cw4-peptide tetrameric complexes and cytolytic assays using target cell pulsed with either peptides. KIR2DL1 binding to these two peptides was measured using surface plasmon resonance and tetramer staining of an NK cell line.


RESULTS
: CTLs could recognize SF9 better than the variant SL9, as shown by both tetramer staining and cytolytic assays. Intriguingly, an HLA-Cw4 tetramer folded with the 'escape' variant SL9 could bind to KIR2DL1 on NK cell lines with higher affinity than HLA-Cw4-SF9. The binding of KIR2DL1 to its ligand results in inhibition of NK cell function. Our results indicate that the HIV-1 gp120 variant peptide SL9 could potentially escape both from NK cell and CTL recognition by increasing its affinity for KIR2DL1 binding.


CONCLUSIONS
These data suggest that HIV-1 can acquire mutations that are capable of escaping from both CTL and NK cell recognition, a phenomenon we have termed 'double escape'.
Thananchai
Hathairat
H
Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Makadzange
Tariro
T
Maenaka
Katsumi
K
Kuroki
Kimiko
K
Peng
Yanchun
Y
Conlon
Chris
C
Rowland-Jones
Sarah
S
Dong
Tao
T
D000915:Antibody Affinity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D054342:Receptors, KIR2DL1 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015699:HIV Envelope Protein gp120; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; C093100:KIR2DL1 protein, human; D054342:Receptors, KIR2DL1