Comprehensive epitope analysis of cross-clade Gag-specific T-cell responses in individuals with early HIV-1 infection in the US epidemic

Vaccine. 2007 Jan 4;25(2):381-90. doi: 10.1016/j.vaccine.2006.07.045. Epub 2006 Aug 10.


To elucidate the mechanisms underlying cross-clade T-cell reactivity, we evaluated responses to Gag peptides based on clades A, B, C, and M-group sequences at the epitope level by IFN-gamma ELISpot assay in 25 subjects following primary clade B infection. T-cell reactivity to CON (consensus), COT (center of tree), and ANC (most recent common ancestor) B peptides was similar and a high level of cross-reactivity was noted to clade A, C, and M-group peptides. T-cell responses to 15 of the 16 epitopes reacted with at least 1 of the 2 heterologous peptides (A or C or both) and 7 epitopes were invariant across all 3 clades. The remaining 9 epitopes were associated with a total of 11 variant sequences, and with the exception of 1, all substitutions were outside the HLA anchor positions. We conclude that Gag-specific cross-clade T-cell responses producing IFN-gamma can be detected in primary HIV-1 infection. Cross-reactivity is attributable to the recognized epitopes being either invariant across clades or differing by single amino acid substitutions outside the HLA anchor sites. Semi-conservative and non-conservative substitutions that presumably involve the T-cell receptor contact sites have significant effects on T-cell recognition. Finally, further studies are needed to determine if the detection of cross-clade IFN-gamma T-cell responses indeed translates to cross-reactive antiviral activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / epidemiology
  • Acquired Immunodeficiency Syndrome / immunology*
  • Adult
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Cross Reactions
  • Epitopes, T-Lymphocyte*
  • Gene Products, gag / immunology*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Time Factors
  • United States / epidemiology


  • Epitopes, T-Lymphocyte
  • Gene Products, gag