Nonionic triblock copolymers facilitate delivery of exogenous proteins into the MHC class I and class II processing pathways

被引:17
作者
Ke, Y
McGraw, CL
Hunter, RL
Kapp, JA
机构
[1] EMORY UNIV, SCH MED, DEPT PATHOL & LAB MED, ATLANTA, GA 30322 USA
[2] EMORY UNIV, SCH MED, WINSHIP CANC CTR, ATLANTA, GA 30322 USA
关键词
D O I
10.1006/cimm.1997.1084
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nonionic triblock copolymers are relatively non-toxic adjuvants that induce high-titer, long-lasting antibody responses. We have previously shown that these adjuvants also induce cell-mediated immunity including lymphokine production by CD4(+) T cells and cytolytic responses by CD8(+) T cells. These copolymers are thought to modulate hydrophobic adhesive interactions between antigens (Ag) and lymphoid cells. We sought to test the hypothesis that copolymers facilitate uptake of exogenous Ag by antigen-presenting cells (APC) using an in vitro model system. Our data show that nonionic triblock copolymers enhanced presentation of soluble ovalbumin (OVA) to the major histocompatibility complex (MHC) class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells, respectively, Presentation of OVA via the class I pathway was enhanced by copolymers in both phagocytic and nonphagocytic APC. However, copolymers did not enhance binding of peptides to the MHC molecules on APC, presentation of endogenously synthesized Ag, or presentation of exogenous Ag delivered by electroporation. These results provide additional evidence that these nonionic triblock copolymers can serve as powerful adjuvants for augmenting both humoral and cell-mediated immunity to protein Ag. (C) 1997 Academic Press.
引用
收藏
页码:113 / 121
页数:9
相关论文
共 44 条
[21]   EFFICIENT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PRESENTATION OF EXOGENOUS ANTIGEN UPON PHAGOCYTOSIS BY MACROPHAGES [J].
KOVACSOVICSBANKOWSKI, M ;
CLARK, K ;
BENACERRAF, B ;
ROCK, KL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (11) :4942-4946
[22]   DELIVERY OF EXOGENOUS ANTIGEN INTO THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II PATHWAYS BY ELECTROPORATION [J].
LI, Y ;
KE, Y ;
GOTTLIEB, PD ;
KAPP, JA .
JOURNAL OF LEUKOCYTE BIOLOGY, 1994, 56 (05) :616-624
[23]   INTRODUCTION OF SOLUBLE-PROTEIN INTO THE CLASS-I PATHWAY OF ANTIGEN PROCESSING AND PRESENTATION [J].
MOORE, MW ;
CARBONE, FR ;
BEVAN, MJ .
CELL, 1988, 54 (06) :777-785
[24]  
NEWMAN MJ, 1992, J IMMUNOL, V148, P2357
[25]   BREFELDIN-A IMPLICATES EGRESS FROM ENDOPLASMIC-RETICULUM IN CLASS-I RESTRICTED ANTIGEN PRESENTATION [J].
NUCHTERN, JG ;
BONIFACINO, JS ;
BIDDISON, WE ;
KLAUSNER, RD .
NATURE, 1989, 339 (6221) :223-226
[26]   PHAGOCYTIC PROCESSING OF BACTERIAL-ANTIGENS FOR CLASS-I MHC PRESENTATION TO T-CELLS [J].
PFEIFER, JD ;
WICK, MJ ;
ROBERTS, RL ;
FINDLAY, K ;
NORMARK, SJ ;
HARDING, CV .
NATURE, 1993, 361 (6410) :359-362
[27]   CAN SOLUBLE-ANTIGENS INDUCE CD8+ CYTOTOXIC T-CELL RESPONSES - A PARADOX REVISITED [J].
RAYCHAUDHURI, S ;
MORROW, WJW .
IMMUNOLOGY TODAY, 1993, 14 (07) :344-348
[28]   INDUCTION OF ANTIGEN-SPECIFIC CLASS-I-RESTRICTED CYTOTOXIC T-CELLS BY SOLUBLE-PROTEINS INVIVO [J].
RAYCHAUDHURI, S ;
TONKS, M ;
CARBONE, F ;
RYSKAMP, T ;
MORROW, WJW ;
HANNA, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (17) :8308-8312
[29]  
REDDY R, 1992, J IMMUNOL, V148, P1585
[30]  
REDDY R, 1991, J IMMUNOL METHODS, V141, P57