HLA tapasin independence: broader peptide repertoire and HIV control
Arman Bashirova, Mathias Viard, Vivek Naranbhai, Alba Grifoni, Wilfredo F. García-Beltrán, Marjan Akdag, Yuko Yuki, Xiaojiang Gao, Colm Ó’hUigín, Malini Raghavan, Steven M. Wolinsky, Jay H. Bream, Priya Duggal, Jeremy Martinson, Nelson L. Michael, Gregory D. Kirk, Susan Buchbinder, David W. Haas, James J. Goedert, Steven G. Deeks, Jacques Fellay, Bruce D. Walker, Philip Goulder, Peter Cresswell, Tim Elliott, Alessandro Sette, Jonathan M. Carlson, Mary Carrington
Abstract
Significance HLA class I molecules bind antigenic peptides and present them on the cell surface to cytotoxic T cells to initiate immune responses. The peptide selection process occurs intracellularly with the aid of a molecule called tapasin. HLA class I molecules are highly variable, which influences their structural characteristics and the level of tapasin involvement in peptide selection. We measured tapasin dependence levels of nearly 100 HLA variants and found that the level of tapasin dependence negatively correlates with the number of peptides that the HLA class I molecule presents to T cells, thereby affecting breadth of the immune response. Analysis of HLA genotypes in HIV cohorts reveals that greater tapasin independence associates with slower disease progression and lower viral load.