Peptide analogs with different affinities for MHC alter the cytokine profile of T helper cells

被引:57
作者
Chaturvedi, P
Yu, Q
Southwood, S
Sette, A
Singh, B
机构
[1] UNIV WESTERN ONTARIO,DEPT MICROBIOL & IMMUNOL,LONDON,ON N6A 5C1,CANADA
[2] UNIV WESTERN ONTARIO,JOHN P ROBARTS RES INST,LONDON,ON N6A 5C1,CANADA
[3] CYTEL CORP,SAN DIEGO,CA 92121
基金
英国医学研究理事会;
关键词
activation; affinity; cytokines; helper cells; MHC binding; peptides;
D O I
10.1093/intimm/8.5.745
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The interaction of the TCR with the immunogenic peptide bound to MHC class II molecules leads to the activation of CD4(+) T helper cells, T helper cells have been divided into two subsets, T(h)1 and T(h)2, on the basis of the cytokines secreted by them, T(h)1 cells which secrete IL-2, IFN-gamma and tumor necrosis factor-beta induce delayed-type hypersensitivity, while T(h)2 cells secreting IL-4, IL-5, IL-6 and IL-10 induce humoral immune response, However, the mechanism of selective activation of T(h)1 and T(h)2 cells in response to different antigens is not fully understood, In this study we examined the selective activation of T(h)1 and T(h)2 cells in response to strongly immunogenic synthetic peptides EYK(EYA)(3), abbreviated as K3; EYK(EYA)(4), abbreviated as K4; and EYKEYAAYA(EYA)(2), abbreviated as K1A2, These peptides are recognized by H-2(d) T cells in the context of I-A(d), and are strongly cross-reactive in both T cell response and antibody response, The peptide K1A2 has very high affinity for I-A(d) while K3 has a much lower affinity, K4 has affinity intermediate between K1A2 and K3, The peptide K1A2 induced T(h)1 and K3 induced T(h)2 cells in BALB/c mice as suggested by their cytokine profiles, K4 induced both T(h)1- and T(h)2-type cytokines. This was also confirmed by the analysis of peptide-specific antibody responses. K3 induced primarily IgG1 response, whereas K4 induced both IgG1 and IgG2a responses in vivo, There was a shift toward a T(h)1-type cytokine profile when K3-primed T cells were challenged with K1A2 in vitro but K1A2-primed cells did not show any shift when challenged with K3, Immunization with higher doses of K3 shifted the response towards T(h)1 type, while immunization with lower doses of K1A2 did not shift the response toward T(h)2. We conclude that cells primed with high-affinity peptide are committed to differentiate into T(h)1 irrespective of the priming dose and affinity of challenge antigen, On the other hand, the differentiation of cells primed with low-affinity peptide depends upon the dose of immunization and binding affinity of the challenge antigen for MHC.
引用
收藏
页码:745 / 755
页数:11
相关论文
共 34 条
  • [1] SYNTHETIC POLYPEPTIDE ANTIGENS OF DEFINED GEOMETRY
    BARTON, MA
    SINGH, B
    FRAGA, E
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1977, 99 (26) : 8491 - 8498
  • [2] Boyer M, 1988, J Mol Recognit, V1, P99, DOI 10.1002/jmr.300010208
  • [3] FUNCTIONAL DEGENERACY OF RESIDUES IN A T-CELL PEPTIDE EPITOPE CONTRIBUTES TO ITS RECOGNITION BY DIFFERENT T-CELL HYBRIDOMAS
    BOYER, M
    NOVAK, Z
    FRAGA, E
    OIKAWA, K
    KAY, CM
    FOTEDAR, A
    SINGH, B
    [J]. INTERNATIONAL IMMUNOLOGY, 1990, 2 (12) : 1221 - 1233
  • [4] BOYER M, 1990, EUR J IMMUNOL, V9, P2145
  • [5] THE RELATION BETWEEN MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) RESTRICTION AND THE CAPACITY OF IA TO BIND IMMUNOGENIC PEPTIDES
    BUUS, S
    SETTE, A
    COLON, SM
    MILES, C
    GREY, HM
    [J]. SCIENCE, 1987, 235 (4794) : 1353 - 1358
  • [6] HIGH ANTIGEN CONCENTRATION INHIBITS T-CELL PROLIFERATION BUT NOT INTERLEUKIN-2 PRODUCTION - EXAMINATION OF LIMITING DILUTION MICROCULTURES AND T-CELL CLONES
    CEREDIG, R
    CORRADIN, G
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1986, 16 (01) : 30 - 34
  • [7] CHER DJ, 1987, J IMMUNOL, V138, P3688
  • [8] 2 TYPES OF MOUSE HELPER T-CELL CLONE .3. FURTHER DIFFERENCES IN LYMPHOKINE SYNTHESIS BETWEEN TH1 AND TH2 CLONES REVEALED BY RNA HYBRIDIZATION, FUNCTIONALLY MONOSPECIFIC BIOASSAYS, AND MONOCLONAL-ANTIBODIES
    CHERWINSKI, HM
    SCHUMACHER, JH
    BROWN, KD
    MOSMANN, TR
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 166 (05) : 1229 - 1244
  • [9] A T(H)1-]T(H)2 SWITCH IS A CRITICAL STEP IN THE ETIOLOGY OF HIV-INFECTION
    CLERICI, M
    SHEARER, GM
    [J]. IMMUNOLOGY TODAY, 1993, 14 (03): : 107 - 110
  • [10] T-CELL RECEPTOR-MHC CLASS-I PEPTIDE INTERACTIONS - AFFINITY, KINETICS, AND SPECIFICITY
    CORR, M
    SLANETZ, AE
    BOYD, LF
    JELONEK, MT
    KHILKO, S
    ALRAMADI, BK
    KIM, YS
    MAHER, SE
    BOTHWELL, ALM
    MARGULIES, DH
    [J]. SCIENCE, 1994, 265 (5174) : 946 - 949