A cytolytic human T lymphocyte clone differentially recognizing HLA-B27 subtypes

Wee, S.; Chen, Li‐Kuang; Grumet, F. Carl; Bowman, Robert J; Taurog, Joel D.

doi:10.1016/0198-8859(84)90089-2

Cited by 18 publications

(5 citation statements)

References 40 publications

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“…Because class I MHC molecules serve as recognition elements for CTL, and because only a small minority of HLA-B27' individuals ever develop B27-associated disease (7,32,33), efforts have been made to identify CTL-defined B27 subtypes that correlate specifically with disease. However, no significant correlation has been found between AS and any particular subtype of B27 (7,9,34), and AS remains most highly correlated with serologically defined B27, just as originally reported in 1973 (9,35,36).…”

Section: Resultsmentioning

confidence: 75%

In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes.

Taurog¹,

El-Zaatari

1988

J. Clin. Invest.

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The HLA class I molecules identified serologically as HLA-B27 are highly associated with ankylosing spondylitis and related human disorders. All known HLA-B27 amino acid sequences contain a cysteine residue at position 67; no other published HLA class I sequence contains a cysteine within the hypervariable region of the a, domain, which extends from amino acid residues 63-84. To investigate the role of this cysteine residue in the antigenic structure of HLA-B27, we isolated a genomic clone encoding a molecule of the HLA-B27.1 subtype and performed oligonucleotide-directed mutagenesis to convert the cysteine at position 67 to a tyrosine. When transfected into mouse L cells, both the wild-type and Cys67 -) Tyr67 mutant B27 genes directed the synthesis and surface expression of molecules reactive with the monomorphic anti-HLA class I antibody W6/32. However, only the L cells transfected with the wild-type B27 gene reacted with the anti-B27 antibody ME1; L cells transfected with the mutant B27 were completely unreactive with this antibody. Experiments with hybrid exons created from the HLA-B27 and HLA-A2 genes yielded results consistent with the mapping of the ME1 epitope to the B27 a, domain. A second anti-B27 antibody, GS145.2, also showed markedly reduced binding to the Cys67 -Tyr67 mutant. These studies document the importance of the unique Cys67 residue in the antigenic structure of HLA-B27.

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Section: Resultsmentioning

confidence: 75%

In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes.

Taurog¹,

El-Zaatari

1988

J. Clin. Invest.

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“…These three variants are specifically defined by cytotoxic B27M2 titer variation on B27 positive cells. Confirmation of these three subdivisions appears likely with HLA-specific killer T lymphocytes (Breuning et al 1982, Breur-Vriesendorp et al 1984, de Waal et al 1985, Miyachi et al 1984, Taurog et al 1985, human alloantisera (de Waal et al 1985), and antivfral killer T lymphocyte studies (Toubert et al 1984). 5) The B27M2 [-] and B27M2Iint] variants are more commonly found in Oriental populations than in Caucasians.…”

Section: A Molecular Model Of Hla-b27mentioning

confidence: 95%

“…Thus, the HLA-B27 antigenic variation originally delineated by serologic reactivity with the monoclonal antibody B27M2 has been confirmed as having true antigenic heterogeneity at the molecular level. Additional confirmation of a B27M2[+] and B27M2 [-] subdivision comes about through the development of a CTL clone (Miyachi et al 1984) with a specificity which correlates almost exactly with the B27M2 antibody reactivity.…”

mentioning

confidence: 97%

“…For example, the striking association between AS and B27 was dependent on the ability to split B27 from the initially cross-reactive and more common B27 antigen. More recently, monoclonal antibodies have succeeded in subdividing B27 (Grumet et al 1981 and further, Breuning et al (1982Breuning et al ( , 1983Breuning et al ( , 1984 and others (Miyachi et al! 1984) have generated cytotoxic T lymphocyte cell lines which also specifically identify subtypes of the HLA-B27 antigen.…”

mentioning

confidence: 99%

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Molecular Variants of the HLA‐B27 Antigen in Healthy Individuals and Patients with Spondylarthropathies

Turek

Grumet

Engleman

1985

Immunological Reviews

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Despite major advances in genetic and structural studies of the HLA-B27 antigen, the underlying mechanism responsible for the remarkable association between this antigen and spondylarthropathies remains unknown. At a molecular level, the use of B27M1 and B27M2 monoclonal antibodies has permitted the identification of distinct allospecific epitopes on the B27 molecule. One of these epitopes, B27M2, is polymorphic and has allowed us to define B27 variants: B27M2[+], B27M2[-], and B27M2[int]. The heterogeneity of the B27 antigen correlates well with biochemical and cytotoxic evidence of genetic heterogeneity. These variants exhibit ethnic variation and also appear to correlate, in preliminary studies, with disease susceptibility, especially among Orientals. HLA gene probing is potentially an even more precise tool than monoclonal antibodies for the study of MHC-related disease susceptibilities. Initial work in our laboratory has resulted in the production of probes with specificity for HLA-B locus genes and current efforts are directed toward the derivation of B27 allele-specific probes. It seems likely that, when such probes are applied to B27-positive individuals, complexity in addition to the B27M2 variants will be revealed. Yet to be defined is the mechanism behind the association between B27 and AS. Is the association causal for disease, or is B27 indeed just a marker for other pathogenic factors somehow linked to it? Available evidence points to both causal and linked roles for B27 in ankylosing spondylitis. Products of both HLA and non-HLA gene families may interact with infectious disease pathogens in susceptible individuals to produce a disorder which may not be specific in its association with any one pathogenic factor.

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“…Human T cell clones. JMAC28 CIL was derived using the priming and cloning protocols as previously described [16], Clones KB36 and KD56 were derived using the protocols described elsewhere [19], Ail the clones were maintained as follows: cloned CTL were seeded at 1x10^ with 1x10^ irradiated (H),(I(K1 rad) LCL 526 in 2 mi of RPMI 1640 (Gibeo Labs. New York.…”

Section: Lymphohlastoid Cell Lines {Lcd Epstein-barrmentioning

confidence: 99%

Loss and Re‐acquisition of Lytic Function by Cloned Cytotoxic T Lymphocytes: Role of Specific Antigen and Interleukin 2

Ochoa¹,

Wee²,

Bach³

1985

Scand J Immunol

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We have previously reported the isolation of 2 human allospecific cytotoxic T-lymphocyte (CTL) clones that can undergo a reversible functional change from a highly lytic phase to a nonlytic quiescent phase and again to a lytic phase. The entire process was found to be regulated by recombinant interleukin 2 (rIL-2). We have now extended these studies in 3 ways. First, we show that specific alloantigens can also function as a signal to reactivate lytic function in the reverted CTL. However, in contrast to CTL reactivated with rIL-2, the antigen-reactivated CTL apparently fail to undergo subsequent cell division. Second, we have also found that this reversion phenomenon is not the same for all CTL tested, as 2 other CTL clones were found that did not revert to the non-lytic phase when cultured for up to 60 h in rIL-2-free medium. Third, the expression of Tac (IL-2 receptor) was also studied throughout the process of reversion and reactivation. rIL-2 added to the cell that had reverted to a non-lytic phase induced, an increase in the expression of Tac receptors during the reactivation phase, to levels greater than those expressed on cells continuously cultured in rIL-2-supplemented medium.

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A cytolytic human T lymphocyte clone differentially recognizing HLA-B27 subtypes

Cited by 18 publications

References 40 publications

In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes.

In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes.

Molecular Variants of the HLA‐B27 Antigen in Healthy Individuals and Patients with Spondylarthropathies

Loss and Re‐acquisition of Lytic Function by Cloned Cytotoxic T Lymphocytes: Role of Specific Antigen and Interleukin 2

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