A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected Thais.

Abstract

BACKGROUND:

CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia.

METHODOLOGY/PRINCIPAL FINDINGS:

To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, (277)YSPVSILDI(285), YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response.

CONCLUSIONS/SIGNIFICANCE:

As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.

• Authors: Supranee Buranapraditkun, Ursula Hempel, Patrawadee Pitakpolrat, Rachel L Allgaier, Pattarawat Thantivorasit, Sven-Iver Lorenzen, Sunee Sirivichayakul, William H Hildebrand, Marcus Altfeld, Christian Brander, Bruce D Walker, Praphan Phanuphak, Pokrath Hansasuta, Sarah L Rowland-Jones, Todd M Allen, Kiat Ruxrungtham
• Journal: PloS one (PLoS One) Vol. 6 Issue 8 Pg. e23603 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21887282 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-C Antigens
• Immunodominant Epitopes
• gag Gene Products, Human Immunodeficiency Virus

Topics

• Adult
• Alleles
• Amino Acid Sequence
• CD8-Positive T-Lymphocytes (immunology)
• Conserved Sequence (genetics)
• Female
• HIV Infections (genetics, immunology)
• HIV-1
• HLA-C Antigens (genetics)
• Humans
• Immunodominant Epitopes (chemistry, immunology)
• Male
• Molecular Sequence Data
• Mutation (genetics)
• Thailand
• gag Gene Products, Human Immunodeficiency Virus (chemistry, immunology)