Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire in humans and human leukocyte antigen-transgenic mice

被引:109
作者
Wentworth, PA
Vitiello, A
Sidney, J
Keogh, E
Chesnut, RW
Grey, H
Sette, A
机构
[1] RW JOHNSON PHARMACEUT RES INST,SAN DIEGO,CA 92121
[2] LA JOLLA INST ALLERGY & IMMUNOL,LA JOLLA,CA
关键词
cytotoxic T lymphocytes; peptides; repertoire; transgenic mice;
D O I
10.1002/eji.1830260115
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2.1/K-b transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the level of overlap between the A2.1-restricted CTL repertoire of A2.1/K-b-transgenic mice and A2.1(+) humans. In both humans and mice, a major histocompatibility complex affinity threshold of approximately 500 nM appears to determine the capacity of a peptide to elicit a CTL response. Good concordance between the human data in vitro and mouse data in vivo was observed with 85% of the high-binding peptides, 58% of the intermediate binders, and 83% of the low/negative binders. Although some peptides immunogenic for mouse CTL but not for humans (and vice versa) could be identified, the data as a whole suggest an extensive overlap between T cell receptor repertoires of mouse and human CTL and support the use of HLA-transgenic mice for the identification of potential human CTL epitopes.
引用
收藏
页码:97 / 101
页数:5
相关论文
共 25 条
[1]  
BOON T, 1994, ANNU REV IMMUNOL, V12, P337, DOI 10.1146/annurev.iy.12.040194.002005
[2]  
CEASE KB, 1994, ANNU REV IMMUNOL, V12, P923, DOI 10.1146/annurev.iy.12.040194.004423
[3]  
ENGELHARD VH, 1994, ANNU REV IMMUNOL, V12, P181, DOI 10.1146/annurev.immunol.12.1.181
[4]   BOTH HUMAN AND MOUSE CELLS EXPRESSING H-2K(B) AND OVALBUMIN PROCESS THE SAME PEPTIDE, SIINFEKL [J].
FALK, K ;
ROTZSCHKE, O ;
FAATH, S ;
GOTH, S ;
GRAEF, I ;
SHASTRI, N ;
RAMMENSEE, HG .
CELLULAR IMMUNOLOGY, 1993, 150 (02) :447-452
[5]  
GERMAIN RN, 1993, ANNU REV IMMUNOL, V11, P403, DOI 10.1146/annurev.iy.11.040193.002155
[6]   MURINE CELLS EXPRESSING AN HLA MOLECULE ARE SPECIFICALLY LYSED BY HLA-RESTRICTED ANTIVIRAL HUMAN T-CELLS [J].
GOMARD, E ;
BEGUE, B ;
SODOYER, S ;
MARYANSKI, JL ;
JORDAN, BR ;
LEVY, JP .
NATURE, 1986, 319 (6049) :153-154
[7]   PEPTIDE TRANSLOCATION BY VARIANTS OF THE TRANSPORTER ASSOCIATED WITH ANTIGEN-PROCESSING [J].
HEEMELS, MT ;
SCHUMACHER, TNM ;
WONIGEIT, K ;
PLOEGH, HL .
SCIENCE, 1993, 262 (5142) :2059-2063
[9]   MOLECULAR ANALYSIS OF THE ASSOCIATION OF HLA-B53 AND RESISTANCE TO SEVERE MALARIA [J].
HILL, AVS ;
ELVIN, J ;
WILLIS, AC ;
AIDOO, M ;
ALLSOPP, CEM ;
GOTCH, FM ;
GAO, XM ;
TAKIGUCHI, M ;
GREENWOOD, BM ;
TOWNSEND, ARM ;
MCMICHAEL, AJ ;
WHITTLE, HC .
NATURE, 1992, 360 (6403) :434-439
[10]   SUPPLY AND TRANSPORT OF PEPTIDES PRESENTED BY CLASS-I MHC MOLECULES [J].
HOWARD, JC .
CURRENT OPINION IN IMMUNOLOGY, 1995, 7 (01) :69-76