HLA tapasin independence: broader peptide repertoire and HIV control
HLA tapasin independence: broader peptide repertoire and HIV control
Human leukocyte antigen (HLA) class I allotypes vary in their ability to present peptides in the absence of tapasin, an essential component of the peptide loading complex. We quantified tapasin dependence of all allotypes that are common in European and African Americans (n = 97), which revealed a broad continuum of values. Ex vivo examination of cytotoxic T cell responses to the entire HIV-1 proteome from infected subjects indicates that tapasin-dependent allotypes present a more limited set of distinct peptides than do tapasin-independent allotypes, data supported by computational predictions. This suggests that variation in tapasin dependence may impact the strength of the immune responses by altering peptide repertoire size. In support of this model, we observed that individuals carrying HLA class I genotypes characterized by greater tapasin independence progress more slowly to AIDS and maintain lower viral loads, presumably due to increased breadth of peptide presentation. Thus, tapasin dependence level, like HLA zygosity, may serve as a means to restrict or expand breadth of the HLA-I peptide repertoire across humans, ultimately influencing immune responses to pathogens and vaccines.
HLA, peptide repertoire, tapasin
28232-28238
Bashirova, Arman A
b6b1a6ce-8939-4cb9-bdbe-a33cc606a536
Viard, Mathias
595419f2-6c43-463e-9f7a-b6f8283bb409
Naranbhai, Vivek
403fc5ea-c33f-45ca-9016-2c6572c19593
Grifoni, Alba
435f9749-ee32-475a-b1d6-edecda5e3015
Garcia-Beltran, Wilfredo
f35a269a-5adf-45e7-b769-3f76a93be8e1
Akdag, Marjan
d9c1a3d6-d665-4b98-bf42-d42824528350
Yuki, Yuko
45f057f8-8a91-4779-ae6c-96e79e1c0497
Gao, Xiaojiang
b62a02d2-1e1b-40c6-8afb-721a2ea851f8
O'hUigin, Colm
b27e26e7-e437-411f-88b9-2f34d60934e4
Raghavan, Malini
6134c046-557a-4b01-a8bd-7d4c1787eff2
Wolinsky, Steven
80a24f0f-f7c2-4441-aab8-51ad7e7cb23b
Bream, Jay H.
4017994c-ba3a-401f-9b3f-5cb2b6c2242c
Duggal, Priya
6308f862-4794-47a5-86b3-39239fd4fcbd
Martinson, Jeremy
13690753-3c6b-4e0d-b496-f524c3d98597
Michael, Nelson L.
8252833c-b6ed-4274-a9be-d24078b09888
Kirk, Gregory D.
562ddcaa-f2c2-4e06-b87e-08e99b0e1244
Buchbinder, Susan P.
25dc1801-4551-4128-aeaa-2498cf46470e
Haas, David
d23548e1-321a-4863-8072-29b0188b8658
Goedert, James J.
d28c5645-6f66-4763-8527-662cde9a8c13
Deeks, Steven G.
9d52ca50-10ed-49e2-838a-baef96df8201
Fellay, Jacques
be4cf13e-1ae6-4e88-85f8-e899f04e2b02
Walker, Bruce
ccc1424e-e694-4119-9a6e-8fa28bc5d9f3
Goulder, Philip
0719cdf3-b4f7-4234-ac5d-cfebc58ffc78
Cresswell, Peter
d577d2b1-60aa-45bf-88aa-522afe2f6467
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Carlson, Jonathan
8857d204-603d-4757-a6f1-0c1202ae8f8d
Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8
Bashirova, Arman A
b6b1a6ce-8939-4cb9-bdbe-a33cc606a536
Viard, Mathias
595419f2-6c43-463e-9f7a-b6f8283bb409
Naranbhai, Vivek
403fc5ea-c33f-45ca-9016-2c6572c19593
Grifoni, Alba
435f9749-ee32-475a-b1d6-edecda5e3015
Garcia-Beltran, Wilfredo
f35a269a-5adf-45e7-b769-3f76a93be8e1
Akdag, Marjan
d9c1a3d6-d665-4b98-bf42-d42824528350
Yuki, Yuko
45f057f8-8a91-4779-ae6c-96e79e1c0497
Gao, Xiaojiang
b62a02d2-1e1b-40c6-8afb-721a2ea851f8
O'hUigin, Colm
b27e26e7-e437-411f-88b9-2f34d60934e4
Raghavan, Malini
6134c046-557a-4b01-a8bd-7d4c1787eff2
Wolinsky, Steven
80a24f0f-f7c2-4441-aab8-51ad7e7cb23b
Bream, Jay H.
4017994c-ba3a-401f-9b3f-5cb2b6c2242c
Duggal, Priya
6308f862-4794-47a5-86b3-39239fd4fcbd
Martinson, Jeremy
13690753-3c6b-4e0d-b496-f524c3d98597
Michael, Nelson L.
8252833c-b6ed-4274-a9be-d24078b09888
Kirk, Gregory D.
562ddcaa-f2c2-4e06-b87e-08e99b0e1244
Buchbinder, Susan P.
25dc1801-4551-4128-aeaa-2498cf46470e
Haas, David
d23548e1-321a-4863-8072-29b0188b8658
Goedert, James J.
d28c5645-6f66-4763-8527-662cde9a8c13
Deeks, Steven G.
9d52ca50-10ed-49e2-838a-baef96df8201
Fellay, Jacques
be4cf13e-1ae6-4e88-85f8-e899f04e2b02
Walker, Bruce
ccc1424e-e694-4119-9a6e-8fa28bc5d9f3
Goulder, Philip
0719cdf3-b4f7-4234-ac5d-cfebc58ffc78
Cresswell, Peter
d577d2b1-60aa-45bf-88aa-522afe2f6467
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Carlson, Jonathan
8857d204-603d-4757-a6f1-0c1202ae8f8d
Carrington, Mary
0fd214c9-4cbc-4719-9d75-9997cd474bd8