HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders

N. Kamikawaji, K. Fujisawa, H. Yoshizumi, M. Fukunaga, M. Yasunami, A. Kimura, Y. Nishimura, Takehiko Sasazuki

Research output: Contribution to journalArticle

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Abstract

We have found that the low immune response to streptococcal cell wall Ag (SCW) was inherited as a dominant trait and was linked to HLA, as deduced from family analysis. In the present report, HLA class II alleles of healthy donors were determined by serology and DNA typing to identify the HLA alleles controlling low or high immune responses to SCW. HLA-DR2-DQR2-DQA1*0102-DQB1*0602(DQw6)-Dw2 haplotype or HLA-DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12 haplotype was increased in frequency in the low responders and the frequency of HLA-DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15 haplotype or HLA-DR9-DRw53-DQA1*0301-DQB1*0303(DQw3)-Dw23 haplotype was increased in the high responders to SCW. Homozygotes of either DQA1*0102 or DQA1*0103 exhibited a low responsiveness to SCW and those of DQA1*0301 were high responders. The heterozygotes of DQA1*0102 or 0103 and DQA1*0301 showed a low response to SCW, thereby confirming that the HLA-linked gene controls the low response to SCW, as a dominant trait. Using mouse L cell transfectants expressing a single class II molecule as the APC, we found that DQw6(DQA1*0103 DQB1*0601) from the low responder haplotype (DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12) activated SCW-specific T cell lines whereas DQw4(DQA1*0301 DQB1*0401) from the high responder haplotype (DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15) did not activate T cell lines specific to SCW. However, DR4 and DR2 presented SCW to CD4+ T cells in both the high and low responders to SCW, hence the DR molecule even from the low responder haplotype functions as an restriction molecule in the low responders. Putative mechanisms linked to the association between the existence of DQ-restricted CD4+ T cells specific to SCW, and low responsiveness to SCW are discussed.

Original languageEnglish
Pages (from-to)2560-2567
Number of pages8
JournalJournal of Immunology
Volume146
Issue number8
Publication statusPublished - Jan 1 1991

Fingerprint

HLA-DQ Antigens
Cell Wall
T-Lymphocytes
Antigens
Haplotypes
HLA-DR2 Antigen
Alleles
HLA-DR4 Antigen
Cell Line
DNA Fingerprinting
Homozygote
Serology
Heterozygote

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kamikawaji, N., Fujisawa, K., Yoshizumi, H., Fukunaga, M., Yasunami, M., Kimura, A., ... Sasazuki, T. (1991). HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders. Journal of Immunology, 146(8), 2560-2567.

HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders. / Kamikawaji, N.; Fujisawa, K.; Yoshizumi, H.; Fukunaga, M.; Yasunami, M.; Kimura, A.; Nishimura, Y.; Sasazuki, Takehiko.

In: Journal of Immunology, Vol. 146, No. 8, 01.01.1991, p. 2560-2567.

Research output: Contribution to journalArticle

Kamikawaji, N, Fujisawa, K, Yoshizumi, H, Fukunaga, M, Yasunami, M, Kimura, A, Nishimura, Y & Sasazuki, T 1991, 'HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders', Journal of Immunology, vol. 146, no. 8, pp. 2560-2567.
Kamikawaji N, Fujisawa K, Yoshizumi H, Fukunaga M, Yasunami M, Kimura A et al. HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders. Journal of Immunology. 1991 Jan 1;146(8):2560-2567.
Kamikawaji, N. ; Fujisawa, K. ; Yoshizumi, H. ; Fukunaga, M. ; Yasunami, M. ; Kimura, A. ; Nishimura, Y. ; Sasazuki, Takehiko. / HLA-DQ-restricted CD4+ T cells specific to streptococcal antigen present in low but not in high responders. In: Journal of Immunology. 1991 ; Vol. 146, No. 8. pp. 2560-2567.
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N2 - We have found that the low immune response to streptococcal cell wall Ag (SCW) was inherited as a dominant trait and was linked to HLA, as deduced from family analysis. In the present report, HLA class II alleles of healthy donors were determined by serology and DNA typing to identify the HLA alleles controlling low or high immune responses to SCW. HLA-DR2-DQR2-DQA1*0102-DQB1*0602(DQw6)-Dw2 haplotype or HLA-DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12 haplotype was increased in frequency in the low responders and the frequency of HLA-DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15 haplotype or HLA-DR9-DRw53-DQA1*0301-DQB1*0303(DQw3)-Dw23 haplotype was increased in the high responders to SCW. Homozygotes of either DQA1*0102 or DQA1*0103 exhibited a low responsiveness to SCW and those of DQA1*0301 were high responders. The heterozygotes of DQA1*0102 or 0103 and DQA1*0301 showed a low response to SCW, thereby confirming that the HLA-linked gene controls the low response to SCW, as a dominant trait. Using mouse L cell transfectants expressing a single class II molecule as the APC, we found that DQw6(DQA1*0103 DQB1*0601) from the low responder haplotype (DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12) activated SCW-specific T cell lines whereas DQw4(DQA1*0301 DQB1*0401) from the high responder haplotype (DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15) did not activate T cell lines specific to SCW. However, DR4 and DR2 presented SCW to CD4+ T cells in both the high and low responders to SCW, hence the DR molecule even from the low responder haplotype functions as an restriction molecule in the low responders. Putative mechanisms linked to the association between the existence of DQ-restricted CD4+ T cells specific to SCW, and low responsiveness to SCW are discussed.

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