Oral Abstract Session 01 - Global HIV Vaccine Enterprise

POSTERS
Posters
Topic 7: Innate Immunity
P07.17 LB
S100A9 Protein is a Novel Ligand for the Receptor
CD85j and Their Interaction is Implicated in the NK
cell-mediated control of HIV-1 Replication
U.Y. Moreno Nieves 1 , V. Arnold 1 , J.S. Cummings 1 , C. Didier 1 ,
A. Gilbert 1 , F. Barré-Sinoussi 1 , D. Scott-Algara 1
1 Institut Pasteur, Paris, France
Background: CD85j is a receptor expressed by different cells of
the human immune system including Natural Killer (NK) cells.
Previous reports have shown that CD85j interacts with several
MHC-I molecules, as well as with some viral proteins (Cosman
D et al., 1997). We have also demonstrated that CD85j + NK
cells efficiently control HIV-1 replication in monocyte-derived
dendritic cells (MDDC) in vitro (Scott-Algara D et al., 2008). We
hypothesize that the CD85j + NK cell-mediated anti-HIV activity
in MDDC is specifically dependent on the interaction between
CD85j receptor and unknown non-HLA class I ligand(s). Therefore
we focused on the identification CD85j ligand(s) and its(their)
implication in the control of HIV-1 infection.
Methods: To identify the CD85j ligand(s), lysates from MDDC
infected or not by HIV-1 were co-immunoprecipitated using
CD85j recombinant receptor and analyzed by SELDI-TOF-MS
protein chip arrays. The interaction between CD85j and its
ligand(s) where then confirmed by ELISA test. Surface expression
of the putative ligand(s) was analyzed by flow cytometry. To
confirm the implication of the interaction receptor-ligand in the
control of HIV replication, NK cells were pre-stimulated with
CD85j ligands and co-cultured with HIV-infected MDDC or CD4 +
T cells, then, intracellular and supernatant p24 were measured.
Results: We found that the CD85j receptor interacts with the
calcium-binding protein S100A9. We further demonstrated
that HIV-1 infection of MDDC modulates the expression of S100
proteins at the surface of MDDC. Pre-stimulation of NK cells
with S100A9 monomers resulted in an increased control of HIV
infection in MDDC and CD4 + T cells. Moreover, pre-stimulation of
NK cells with S100A9 tetramers resulted in a better and increased
control of HIV-1 infection in CD4 + T cells.
Conclusion: Triggering the inhibitory receptor CD85j on NK cells
by S100A9 may be implicated in the establishment and/or the
regulation of the specific anti-HIV-1 NK cell response.
188
AIDS Vaccine 2012
P07.18 LB
Are the KIR3DS1homozygous and
KIR3DL1*h/*y+HLA-B*57 Genotypes Associated
Protection From HIV by Different Routes of
Exposure?
B. Tallon 2 , J. Bruneau 1 , C.M. Tsoukas 2 , J. Routy 2 , N.F. Bernard 2
1 Centre de Recherche du Centre Hospitalier de l’Université de
Montréal, Canada; 2 Research Institute McGill University Health
Center, Montreal, Canada
Background: We previously reported that HIV Exposed
Seronegative (HESN) individuals have a higher frequency than
HIV infected subjects of 2 genotypes: homozygosity for Killer
Immunoglobulin-like Receptor (KIR) 3DS1 (KIR3DS1hmz) and
homozygosity for high expression KIR3DL1 genotypes co-expressed
with HLA-B*57 (*h/*y+B*57). KIR3DL1/S1 are Natural Killer (NK)
cell receptors that influence NK functionality. Here, we assessed
whether these genotypes were associated with protection by
parenteral and mucosal routes of HIV exposure.
Methods: 473 Caucasian individuals were typed for HLA, KIR3DL1/
S1 generic genotypes and KIR3DL1 allotypes. Of 88 HESN, n=69
were injection drug users (IDU) and 19 were sexually exposed
(sHESN). Of 385 HIV seropositive subjects n=108 were IDU and
n=277 were infected through sexual exposure. The frequency of
KIR3DS1hmz and *h/*y+B*57 carriers was compared in HESN
versus HIV susceptible subjects exposed through parenteral
versus mucosal routes.
Results: KIR3DS1hmz were more frequent among HESN than
HIV positive IDU (10% versus 2.7%, respectively, p=0.05). This
genotype was also more frequent among HESN than HIV infected
individuals exposed sexually (25% versus 5.7%, respectively,
p