Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses

被引:130
作者
Bihl, Florian
Frahm, Nicole
Di Giammarino, Loriana
Sidney, John
John, Mina
Yusim, Karina
Woodberry, Tonia
Sango, Kaori
Hewitt, Hannah S.
Henry, Leah
Linde, Caitlyn H.
Chisholm, John V., III
Zaman, Tauheed M.
Pae, Eunice
Mallal, Simon
Walker, Bruce D.
Sette, Alessandro
Korber, Bette T.
Heckerman, David
Brander, Christian
机构
[1] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA
[2] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
[3] Murdoch Univ, Perth, WA, Australia
[4] Los Alamos Natl Lab, Los Alamos, NM 87545 USA
[5] Menzies Sch Hlth Res, Darwin, NT, Australia
[6] Fenway Community Hlth Ctr, Boston, MA 02115 USA
[7] Microsoft Res, Redmond, WA 98052 USA
关键词
D O I
10.4049/jimmunol.176.7.4094
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or the strongest response within a single individual, yet factors determining either inter- or intraindividual immunodominance are still poorly understood. More than 90 individuals were tested against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes were significantly more frequently recognized than HLA-A- or HLA-C-restricted epitopes. HLA-B-restricted epitopes also induced responses of higher magnitude than did either HLA-A- or HLA-C-restricted epitopes, although this comparison only reached statistical significance for EBV epitopes. For both viruses, the magnitude and frequency of recognition were correlated with each other, but not with the epitope binding affinity to the restricting HLA allele. The presence or absence of HIV coinfection did not impact EBV epitope immunodominance patterns significantly. Peptide titration studies showed that the magnitude of responses was associated with high functional avidity, requiring low concentration of cognate peptide to respond in in vitro assays. The data support the important role of HLA-B alleles in antiviral immunity and afford a better understanding of the factors contributing to inter- and intraindividual immunodominance.
引用
收藏
页码:4094 / 4101
页数:8
相关论文
共 48 条
[1]  
Alexander J, 1997, J IMMUNOL, V159, P4753
[2]   The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: Implications for vaccine design [J].
Altfeld, M ;
Allen, TM ;
Kalife, ET ;
Frahm, N ;
Addo, MM ;
Mothe, BR ;
Rathod, A ;
Reyor, LL ;
Harlow, J ;
Yu, XG ;
Perkins, B ;
Robinson, LK ;
Sidney, J ;
Alter, G ;
Lichterfeld, M ;
Sette, A ;
Rosenberg, ES ;
Goulder, PJR ;
Brander, C ;
Walker, BD .
JOURNAL OF VIROLOGY, 2005, 79 (08) :5000-5005
[3]   Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif [J].
Altfeld, MA ;
Livingston, B ;
Reshamwala, N ;
Nguyen, PT ;
Addo, MM ;
Shea, A ;
Newman, M ;
Fikes, J ;
Sidney, J ;
Wentworth, P ;
Chesnut, R ;
Eldridge, RL ;
Rosenberg, ES ;
Robbins, GK ;
Brander, C ;
Sax, PE ;
Boswell, S ;
Flynn, T ;
Buchbinder, S ;
Goulder, PJR ;
Walker, BD ;
Sette, A ;
Kalams, SA .
JOURNAL OF VIROLOGY, 2001, 75 (03) :1301-1311
[4]  
[Anonymous], 2000, The HLA Facts Book
[5]  
Bihl FK, 2005, J TRANSL MED, V3
[6]   Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV-1CTL epitope Gag77-85 [J].
Boggiano, C ;
Moya, R ;
Pinilla, C ;
Bihl, F ;
Brander, C ;
Sidney, J ;
Sette, A ;
Blondelle, SE .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2005, 35 (05) :1428-1437
[7]   Preferential HLA usage in the influenza virus-specific CTL response [J].
Boon, ACM ;
de Mutsert, G ;
Fouchier, RAM ;
Sintnicolaas, K ;
Osterhaus, ADME ;
Rimmelzwaan, GF .
JOURNAL OF IMMUNOLOGY, 2004, 172 (07) :4435-4443
[8]   Early and late cytotoxic T lymphocyte responses in HIV infection [J].
Brander, C ;
Rivière, Y .
AIDS, 2002, 16 :S97-S103
[9]   Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection [J].
Brander, C ;
Hartman, KE ;
Trocha, AK ;
Jones, NG ;
Johnson, RP ;
Korber, B ;
Wentworth, P ;
Buchbinder, SP ;
Wolinsky, S ;
Walker, BD ;
Kalams, SA .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (11) :2559-2566
[10]   Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein [J].
Brander, C ;
O'Connor, P ;
Suscovich, T ;
Jones, NG ;
Lee, Y ;
Kedes, D ;
Ganem, D ;
Martin, J ;
Osmond, D ;
Southwood, S ;
Sette, A ;
Walker, BD ;
Scadden, DT .
JOURNAL OF INFECTIOUS DISEASES, 2001, 184 (02) :119-126