1995
DOI: 10.1002/eji.1830251213
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Altered Th1/Th2 balance associated with the immunosuppressive/protective effect of the H‐2Ab allele on the response to allo‐4‐hydroxyphenylpyruvate dioxygenase

Abstract: The H-2Ab allele exerts a dominant down-regulatory effect on the anti-allo-HPPD (4-hydroxyphenylpyruvate dioxygenase) antibody response, through a hitherto unknown mechanism. In the present study, the allo-variable peptide bound to responder H-2Ak molecules with higher affinity than to H-2Ab ones, arguing against the operation of an affinity hierarchy. Quantitative polymerase chain reaction revealed differences in cytokine mRNA expression between suppressed and high-responder mice. Lymph node cells of responde… Show more

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Cited by 30 publications
(24 citation statements)
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“…Recent work suggests that the MHC molecule may also bind to the T cell receptor in an effective but apparently nonspecific manner (38), possibly involving self peptides; this may deliver a survival signal to the T cell (39)(40)(41). This apparently nonspecific signaling might account for the otherwise puzzling observation that the H-2A b molecule, although able to suppress the anti-allo-4-hydroxyphenylpyruvate dioxygenase (HPPD) response, does not bind the relevant allopeptide to a detectable extent (9).…”
Section: Resultsmentioning
confidence: 99%
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“…Recent work suggests that the MHC molecule may also bind to the T cell receptor in an effective but apparently nonspecific manner (38), possibly involving self peptides; this may deliver a survival signal to the T cell (39)(40)(41). This apparently nonspecific signaling might account for the otherwise puzzling observation that the H-2A b molecule, although able to suppress the anti-allo-4-hydroxyphenylpyruvate dioxygenase (HPPD) response, does not bind the relevant allopeptide to a detectable extent (9).…”
Section: Resultsmentioning
confidence: 99%
“…In contrast, the I-A d and I-A k alleles are neutral, i.e., have not been found to exert a suppressive effect on antibody responses, whereas I-A q is a positive response gene in CIA and has not otherwise been tested for suppressive activity. All of these effects are dominant, in that the presence of a single copy of the gene is sufficient to obtain the suppressive͞protective effect (4,9). They represent no more than a bias, because each of these genes can also serve as a positive response gene for other antigens.…”
mentioning
confidence: 99%
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“…Crosses with naturally C5-deficient mice indicate that an intact C5 gene is required for the disease to develop (10). Furthermore, substitution in the MHC of a class II allele that suppresses the early burst of IL-4 production partially protects against the disease, in accordance with the need for this early burst as demonstrated by treatment of mice with anti-IL-4 monoclonal antibody (11,12).…”
mentioning
confidence: 83%
“…Back in the 1970's two groups, one in Prague and the other in Boston (reviewed in [43]) noted that H2 b mice and their F1 hybrids make a defective response to sheep red blood cells and to singleprotein antigens [44], and are also slightly resistant to induction of collagen-induced arthritis [45,46]. Using MHC congenic and recombinant mouse strains, the dominant effect could be pinned down to the H2-Ab b allele driving Th1 polarisation [47], although with at least two other unlinked genes having a similar effect in C57BL mice, one has to be cautious [48,49].…”
Section: I) Murinementioning
confidence: 99%