Vaccine-induced HIV-specific CD8+ T cells utilize preferential HLA alleles and target-specific regions of HIV-1

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 06/2011; 58(3):248-52. DOI: 10.1097/QAI.0b013e318228f992
Source: PubMed


Most T cell-based HIV-1 vaccine candidates induce responses of limited breadth for reasons that are unclear. We evaluated vaccine-induced T-cell responses in individuals receiving an HIV-1 recombinant adenoviral vaccine. Certain HLA alleles (B27, B57, B35, and B14) are preferentially utilized to mount HIV-specific responses, whereas other alleles (A02 and B07) are rarely utilized (P < 0.001). This preference seems due to 4 following factors individually or in combination: higher affinity of specific peptides to specific HLA alleles; higher avidity of T-cell receptor; HLA and peptide interaction; and/or higher surface expression of certain HLA. Thus, HLA immunodominance plays a substantial role in vaccine-induced T-cell responses.

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    • "Non-synonymous allelic variants of HLA gene products can bind distinct antigenic peptides [10,11], be subject to differential regulation [12,13], and have varied interactions with T-Cell Receptors [14], Killer Immunoglobulin-like Receptors[15] and viral proteins [16]. The direct link between HLA polymorphism and various diseases is a subject of intensive investigation, with hundreds of published studies every year. "
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