Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC).
BACKGROUND
The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC), which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP) covering the whole concensus clades B and C proteome.


RESULTS
The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413) of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574) can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm3 were observed when compared to those with less than 200/mm3 or more than 400/mm3, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load.


CONCLUSIONS
This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were demonstrated with clade B infected populations. The immunodominant regions identified in this population can facilitate future HIV-1 vaccine development in China.
Chen
Jianping
J
State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China. jping_chen@chinaaids.cn
Hong
Kunxue
K
Jia
Mingming
M
Liu
Hongwei
H
Zhang
Yuanzhi
Y
Liu
Sha
S
Zhang
Xiaoqing
X
Zhao
Hongjing
H
Peng
Hong
H
Ma
Pengfei
P
Xing
Hui
H
Ruan
Yuhua
Y
Williams
Katie L
KL
Yu
Xu G
XG
Altfeld
Marcus
M
Walker
Bruce D
BD
Shao
Yiming
Y
D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D002681:China; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D020543:Proteome / Q000276:immunology; D015819:Substance Abuse, Intravenous / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D020543:Proteome; D007371:Interferon-gamma