Inter-clade cross-reactivity of HIV-1-specific T cell responses in human immunodeficiency virus type 1 infection in China.
To determine the degree of HIV-1-specific cytotoxic-T-lymphocyte (CTL) cross-responses to the clade B and C consensus sequences at the single peptide level. We assessed CTL responses in 46 HIV-1 clade B chronically infected individuals using an interferon-gamma Elispot assay with a total of 826 overlapping peptides spanning HIV-1 clade B and C consensus sequences. In general, 583 peptides were recognized by HIV-1-specific T cells in the study subjects (292 clade B, 291 clade C respectively), of which 204 peptides in both clades were recognized simultaneously. The HIV-1-specific CTL responses to both clade peptides contributed 54.23% (954/1759) to the total responses. No significant difference was observed between the overall magnitude or frequency of CTL responses to clade B proteins and those to clade C proteins. According to the profiles of CTL magnitude and CTL frequency, the top 44 and 35 synthetic peptides were identified as immunodominant regions in the clade B and C consensus sequences respectively and 27 corresponding peptides in two immunodominant regions were cross-reactive. These peptides with cross-reactivity had a significantly higher ability to elicit CTL responses (P< 0.01) and preferentially had a trend of lower entropy and higher inter-clade homology. A wide degree of cross-clade reactivity of HIV-1-specific T cells exist in clade B and clade C variants. Most of immunodominant peptides with cross-reactivity are vigorous to elicit CTL responses and preferentially be conservative. This result may make future HIV-1 vaccines including multiple copies of CTL epitopes in these immunodominant peptides effective for this population.
Zhao
Shuguang
S
Department of Infectious Diseases, Tangdu Hospital Affiliated to the Fourth Military Medical University, Xi'an, PR China.
Zhai
Song
S
Zhuang
Yan
Y
Wang
Shaoyang
S
Huang
Dedong
D
Kang
Whenzhen
W
Li
Xinhong
X
Yu
Xu G
XG
Walker
Bruce D
BD
Altfeld
Marcus A
MA
Sun
Yongtao
Y
D000328:Adult; D002681:China; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000145:classification*; D005260:Female; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D012191:Retroviridae Proteins / Q000096:biosynthesis / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology*
D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D012191:Retroviridae Proteins