THE REQUIREMENT FOR DM IN CLASS II-RESTRICTED ANTIGEN PRESENTATION AND SDS-STABLE DIMER FORMATION IS ALLELE-DEPENDENT AND SPECIES-DEPENDENT

被引:105
作者
STEBBINS, CC
LOSS, GE
ELIAS, CG
CHERVONSKY, A
SANT, AJ
机构
[1] UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637
[2] UNIV CHICAGO,COMM IMMUNOL,CHICAGO,IL 60637
[3] UNIV CHICAGO,DEPT SURG,CHICAGO,IL 60637
关键词
D O I
10.1084/jem.181.1.223
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recently several cell lines have been identified with mutations in a major histocompatibility complex (MHC)-linked protein that lead to defects in class II-restricted antigen presentation and a defect in the formation of class II SDS-stable dimers. The defect in these cells has recently been shown to result from the inability to express the MHC-encoded nonclassical class II molecule called DM. To further examine the role of DM in class II-restricted antigen presentation, we asked if this defect would equally affect different allelic and species variants of class II molecules. To investigate this, we transfected the parent cell lines T1 and 8.1.6 and their respective antigen presentation mutants T2 and 9.5.3 with the genes encoding I-A(d) and examined the derived transfectants for their ability to present antigen, the conformation of I-A(d) to associate and dissociate with Ii. Surprisingly, these studies also revealed that the antigen presentation defect observed for DR in the 9.5.3 cells did not compromise I-A(d)-restricted antigen presentation. In addition, we found that the level of SDS-stable dimer formation did not correlate with antigen presentation capacity for I-A(d) and that the amount of SDS-stable I-A(d) dimer depends on the cellular context in which the class II molecule is expressed. Our results suggest that the ability to form SDS-stable dimer is not strictly correlated with class II-restricted antigen presentation. Finally, when two allelic forms of murine class II molecules were compared in the defective T2 cell line, it was found that I-A(k) but not I-A(d) forms SDS-stable dimers equivalent to that seen in the parental cell lines. Overall, our results suggest that DM may modulate rather than play a requisite role in I-A(d)-restricted antigen presentation and SDS-stable dimer formation and that dependency on DM may be allele or species specific.
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页码:223 / 234
页数:12
相关论文
共 50 条
[1]   TRANSIENT ACCUMULATION OF NEW CLASS-II MHC MOLECULES IN A NOVEL ENDOCYTIC COMPARTMENT IN B-LYMPHOCYTES [J].
AMIGORENA, S ;
DRAKE, JR ;
WEBSTER, P ;
MELLMAN, I .
NATURE, 1994, 369 (6476) :113-120
[2]   INVARIANT CHAIN CAN FUNCTION AS A CHAPERONE PROTEIN FOR CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES [J].
ANDERSON, MS ;
MILLER, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (06) :2282-2286
[3]   CORRELATION BETWEEN INVARIANT CHAIN EXPRESSION LEVEL AND CAPABILITY TO PRESENT ANTIGEN TO MHC CLASS II-RESTRICTED T-CELLS [J].
BERTOLINO, P ;
FORQUET, F ;
PONT, S ;
KOCH, N ;
GERLIER, D ;
RABOURDINCOMBE, C .
INTERNATIONAL IMMUNOLOGY, 1991, 3 (05) :435-443
[4]  
BRAUNSTEIN NS, 1990, J IMMUNOL, V145, P1635
[5]  
CEMAN S, 1994, J IMMUNOL, V152, P2865
[6]   SPECIFICITY AND PROMISCUITY AMONG NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR ALLELES [J].
CHICZ, RM ;
URBAN, RG ;
GORGA, JC ;
VIGNALI, DAA ;
LANE, WS ;
STROMINGER, JL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (01) :27-47
[7]   PREDOMINANT NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR1 ARE DERIVED FROM MHC-RELATED MOLECULES AND ARE HETEROGENEOUS IN SIZE [J].
CHICZ, RM ;
URBAN, RG ;
LANE, WS ;
GORGA, JC ;
STERN, LJ ;
VIGNALI, DAA ;
STROMINGER, JL .
NATURE, 1992, 358 (6389) :764-768
[8]  
CLARK E, 1984, LEUKOCYTE TPING
[9]  
COTNER T, 1993, J IMMUNOL, V146, P414
[10]   PROCESSED ANTIGEN BINDS TO NEWLY SYNTHESIZED MHC CLASS II MOLECULES IN ANTIGEN-SPECIFIC LYMPHOCYTES-B [J].
DAVIDSON, HW ;
REID, PA ;
LANZAVECCHIA, A ;
WATTS, C .
CELL, 1991, 67 (01) :105-116