[HTML][HTML] CD8+ T-cell cytotoxic capacity associated with human immunodeficiency virus-1 control can be mediated through various epitopes and human leukocyte …

SA Migueles, D Mendoza, MG Zimmerman… - …, 2015 - thelancet.com
SA Migueles, D Mendoza, MG Zimmerman, KM Martins, SA Toulmin, EP Kelly, BA Peterson…
EBioMedicine, 2015thelancet.com
Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1
replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should
inform the design of efficacious HIV vaccines and immunotherapies. Durable control in
LTNP/EC is likely mediated by highly functional virus-specific CD8+ T-cells. Protective
Human Leukocyte Antigen (HLA) class I alleles, like B* 27 and B* 57, are present in most,
but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV …
Abstract
Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8+ T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B*27 and B*57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV-specific immune responses. To better understand the contribution of epitope targeting and conservation to immune control, we compared the CD8+ T-cell specificity and function of B*27/57neg LTNP/EC (n=23), B*27/57pos LTNP/EC (n=23) and B*27/57neg progressors (n=13). Fine mapping revealed 11 previously unreported immunodominant responses. Although B*27/57neg LTNP/EC did not target more highly conserved epitopes, their CD8+ T-cell cytotoxic capacity was significantly higher than progressors. Similar to B*27/57pos LTNP/EC, this superior cytotoxicity was mediated by preferential expansion of immunodominant responses and lysis through the predicted HLA. These findings suggest that increased CD8+ T-cell cytotoxic capacity is a common mechanism of control in most LTNP/EC regardless of HLA type. They also suggest that potent cytotoxicity can be mediated through various epitopes and HLA molecules and could, in theory, be induced in most people.
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