HLA-DR PEPTIDE-INDUCED ALLOREACTIVE T-CELL LINES REVEAL AN HLA-DR SEQUENCE THAT CAN BE BOTH DOMINANT AND CRYPTIC - EVIDENCE FOR ALLELE-SPECIFIC PROCESSING

被引:13
作者
DEKOSTER, HS [1 ]
VANROOD, JJ [1 ]
TERMIJTELEN, A [1 ]
机构
[1] UNIV HOSP LEIDEN,BLOOD BANK,2300 RC LEIDEN,NETHERLANDS
关键词
D O I
10.1002/eji.1830220628
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previously, we reported on a T cell line, ThoU6, which we obtained through stimulation of DPw3+ cells with a synthetic "DR3 peptide" with a sequence identical to the third hypervariable region of the DRB1*0301 chain. This T cell line recognizes both the synthetic peptide presented by DPw3 as well as DR3+ DPw3+ stimulator cells. This implies that the synthetic DR3 peptide has a natural counterpart in DR3-positive cells. Here we describe the recognition pattern of another T cell line that was sensitized with the same synthetic DR3 peptide. This T cell line, BieU6, shows both HLA-DRw13/Dw18 (self)-restricted recognition of the synthetic DR3 peptide and allorecognition towards DR13/Dw19, a molecule which is highly homologous to Dw18, in the absence of synthetic peptide. These results suggest that the epitope formed by the Dw18 molecule plus the synthetic DR3 peptide and recognized by T cell line BieU6 mimics the Dw19 molecule. The potential role for a Dw19-specific peptide is discussed. The inability of T cell line BieU6 to recognize Dw18+ DR3+ cells indicates that, in this case, the synthetic DR3 peptide is "cryptic", i.e. does not have a natural counterpart that is effectively presented to Tcells. Mapping of the shortest peptides recognized by T cell lines ThoU6 and BieU6 indicate that these sequences are fully overlapping. We, therefore, suggest that the antigen-presenting molecules, HLA-DPw3 and HLA-Dw18, differ in their accessibility for self peptides derived from the third hypervariable region of DR molecules. These observations may be explained by allele-specific processing.
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页码:1531 / 1539
页数:9
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共 50 条
[1]   CORRELATION BETWEEN CD8 DEPENDENCY AND DETERMINANT DENSITY USING PEPTIDE-INDUCED, LD-RESTRICTED CYTOTOXIC LYMPHOCYTES-T [J].
ALEXANDER, MA ;
DAMICO, CA ;
WIETIES, KM ;
HANSEN, TH ;
CONNOLLY, JM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 173 (04) :849-858
[2]  
ANDERSON DC, 1988, J IMMUNOL, V141, P607
[3]  
BARANY G, 1980, PEPTIDES ANAL SYNTHE, V2, P1
[4]   ALLELIC VARIATION IN THE DR SUBREGION OF THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX [J].
BELL, JI ;
DENNEY, D ;
FOSTER, L ;
BELT, T ;
TODD, JA ;
MCDEVITT, HO .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (17) :6234-6238
[5]   IMMUNOGENICITY AND TOLEROGENICITY OF SELF-MAJOR HISTOCOMPATIBILITY COMPLEX PEPTIDES [J].
BENICHOU, G ;
TAKIZAWA, PA ;
HO, PT ;
KILLION, CC ;
OLSON, CA ;
MCMILLAN, M ;
SERCARZ, EE .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (05) :1341-1346
[6]   KILLER CELLS REACTIVE TO ALTERED-SELF ANTIGENS CAN ALSO BE ALLOREACTIVE [J].
BEVAN, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (05) :2094-2098
[7]   INDUCTION OF CYTO-TOXIC LYMPHOCYTES-T BY PRIMARY INVITRO STIMULATION WITH PEPTIDES [J].
CARBONE, FR ;
MOORE, MW ;
SHEIL, JM ;
BEVAN, MJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1988, 167 (06) :1767-1779
[8]  
CARROLL PG, 1979, TRANSPL P, V11, P1809
[9]   T-CELLS SENSITIZED TO SYNTHETIC HLA-DR3 PEPTIDE GIVE EVIDENCE OF CONTINUOUS PRESENTATION OF DENATURED HLA-DR3 MOLECULES BY HLA-DP [J].
DEKOSTER, HS ;
ANDERSON, DC ;
TERMIJTELEN, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 169 (03) :1191-1196
[10]   CELLULAR PEPTIDE COMPOSITION GOVERNED BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES [J].
FALK, K ;
ROTZSCHKE, O ;
RAMMENSEE, HG .
NATURE, 1990, 348 (6298) :248-251