Clonal heterogeneity of HLA-B27 cellular allo-recognition. Delineation of immunodominant sites

Aparicio, Pedro; Jaraquemada, Dolores; Rojo, Susana; Castro, José A. Łópez de

doi:10.1002/eji.1830180204

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…Comparison of the sequence profiles of the peptide pools from B'2701 to B~ suggests that B27 subtypes share a significant number of bound peptides, but many R2containing peptides either bind to only some subtypes or they bind to all the subtypes but with greatly different efficiency. This is in agreement with functional studies showing frequent crossreactivity, but also differential recognition, of HLA-B27 subtypes with anti-B~ CTL (14,23). Substantial differences among peptide pools from two HL.A-A2 subtypes have also been recently reported (24).…”

Section: Discussionsupporting

confidence: 89%

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

Rojo

Garcı́a

Villadangos

et al. 1993

The Journal of Experimental Medicine

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SummaryHLA-B27 subtypes share many structural features, including their pocket ]3, which interacts with a conserved Arg residue at the second position of B*2705-bound peptides. Subtypes differ among each other at other locations in the peptide binding site. In this study, metabolic labeling and radiochemical pool sequencing were used to address the following issues: (a) presence of the Arg 2 (R2) motif among peptides bound to the various HLA-B27 subtypes; (b) influence of mutations inside and outside pocket B on this motif; and (c) the degree of similarity among the peptide pools bound to the various B27 subtypes. Sequencing of Arg-labeled peptide pools extracted from B'2701 to B'2706, and from two site-directed mutants ofB'2705 with changes outside pocket B, indicated that all of these molecules bind peptides with Arg at position 2. Peptides from several mutants with changes altering the structure of pocket 13, and from one mutant at the pocket B rim, also retained the lk2 motif. However, this was absent in the peptide pool extracted from the M45 mutant, in which the negative charge of pocket B, conferred to HLA-B27 by Glu45, was canceled. These results indicate that alterations outside pocket B, and even disruption of the network of hydrogen bonds that stabilizes Arg binding in pocket B, do not impair binding of peptides bearing the R2 motif, but a nonconservative substitution at position 45 does. As a substantial fraction of anti-B ~ cytotoxic T lymphocyte (CTL) clones crossreact with the M45 mutant (Villadangos, J., B. Galocha, D. L6pez, V. Cairo, andJ.A. L6pez de Castro. 1992.J. Irnraunol. 149:505) this result suggests that determinant mimicry by nonidentical peptides may frequently account for unexpected CTL crossreactions. Metabolic labeling with various other amino acids and radiochemical sequencing revealed similarities, but also substantial differences, among the peptide pools from the various HLA-B27 subtypes. This strongly suggests that many peptides bind to multiple subtypes, but significant subsets of peptides bound to a given HLA-B27 subtype do not bind to other subtypes or do so with greatly altered effidency. These results indicate the importance of polymorphism outside pocket B in modulating peptide binding to HLA-B27.

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Section: Discussionsupporting

confidence: 89%

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

Rojo

Garcı́a

Villadangos

et al. 1993

The Journal of Experimental Medicine

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“…In previous studies we have established the fine specificity of a series of anti-B27 CTL clones derived from individual PA in this and other experiments 19,10,191. On the bases of the some individual anti-B27 CTL clones is abrogated by changes located at opposites ends of this site, such as residues 59 and 152 [9,10 Similar observations have been reported for some anti-H-2K alloreactive CTL clones that fail to recognize somatic mutants with changes located far apart on the surface of the peptide-binding groove [34].…”

Section: Discussionmentioning

confidence: 95%

“…In previous studies we have characterized a series of alloreactive CTL clones derived from a single B27-individual after stimulation with B*2705+ (B27.1') cells [9,10,191. A common feature of these clones was their lack of recognition of those HLA-B27 subtypes with a change at residue 152 (B*2704 and B*2706) as well as their lower or null recognition of B*2702, with changes at positions 77,80 and 81 with respect to B*2705.…”

Section: Introductionmentioning

confidence: 99%

Modulation on immunogenicity by HLA‐B27 subtype polymorphism

et al. 1988

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Cells from the same HLA-B27- individual, PA, were stimulated in vitro in primary mixed lymphocyte culture, with either B*2705+ or B*2704+ lymphoblastoid cell lines, in independent experiments. Cytolytic T lymphocytes (CTL) were cloned at limiting dilution and the clones obtained were screened for anti-B27 alloreactivity. Most of the CTL clones generated against the B*2705+ stimulator cells were directed against the B*2705 antigen. In contrast, no anti-B27 CTL clones were found among those derived against the B*2704+ stimulator cells. This was not due to a poor cytotoxic response against these cells because a large proportion of the T cell clones derived from this stimulation were cytotoxic. B2704 differs from B*2705 by only two amino acid changes at positions 77 and 152. Previous studies (Aparacio, P. et al., Eur. J. Immunol. 1988.18: 203) have shown that none of the anti-B*2705 CTL clones derived from donor PA and amenable to detailed characterization cross-reacted with B*2704, suggesting that most of this cytotoxic response was directed against an immunodominant determinant contributed for by residues 77 and/or 152 from B*2705. The present results further suggest that the changes at these positions in B*2704 alter this determinant in such a way that B*2704 becomes less immunogenic for the particular individual PA. Furthermore, a similar poor anti-B*2704 CTL response was obtained from a second B27- responder individual, AE, stimulated with another B2704+ cell line. The single anti-B*2704 CTL clone, 64.8P, isolated from this second individual, displayed an unusual reaction pattern in that it cross-reacted with all B27 subtypes with changes only at or close to positions 77 and 152, including B*2705. Significantly, the only HLA-B27 subtype that was not recognized by CTL 64.8P was B*2703, which differs from B*2705 only at residue 59. This residue is located in the three-dimensional structure at the opposite end from residues 77 and 152 at the surface of the antigen-binding groove of the class I molecule. Thus, the area around residues 77 and 152 is not an essential part of the epitope recognized by CTL 64.8P.

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“…On the other hand, the serological cross-reactivities between HLA-B27 and -B40 are known. 13 Other HLA-B27 cross-reactive haplotypes are -B7, -B42, and -B60, which are all known frequently to be positive in patients with -B27-negative ReA in the United States and in Europe. Robinson et al 14 reported a high incidence of -B40 in HLA-B27-positive ankylosing spondylitis patients in the United States.…”

Section: Discussionmentioning

confidence: 99%

Reactive arthritis after pharyngeal infection: report of two siblings

Asakawa¹,

Torikoe²,

Kondo³

et al. 2002

Modern Rheumatology

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In this report we describe the cases of two siblings with reactive arthritis (ReA) induced by pharyngeal infections. The patients were a man and his sister living with their parents. He developed arthritis in August 1997, and his younger sister developed similar symptoms in September 1998. Their disease conditions were both severe and required hospitalization. Their conditions improved with the administration of nonsteroidal anti-inflammatory drugs together with antibiotics, and both fully recovered within 1-2 weeks. Rheumatic fever was ruled out since streptococcal infections were not demonstrated with antistreptolysin O (ASO) or antistreptokinase (ASK) titers, or with pharyngeal culture. The sister suffered from a rash which was similar to erythema nodosum on her lower extremities, but neither chorea nor carditis was observed. Both human leukocyte antigen (HLA) typing analyses revealed positive results for HLA-B40 and -B39 for the brother and sister, respectively. Both HLA-B40 and -B39 are considered to be related to HLA-B27-negative ReA, most likely poststreptococcal reactive arthritis (PSRA). Therefore, the two patients were tentatively diagnosed as suffering from PSRA.Key words Group-A streptococcal infection · Human leukocyte antigen (HLA)-B27, 39, 40 · Human leukocyte antigen (HLA) typing · Reactive arthritis (ReA)

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Clonal heterogeneity of HLA-B27 cellular allo-recognition. Delineation of immunodominant sites

Cited by 9 publications

References 34 publications

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

Modulation on immunogenicity by HLA‐B27 subtype polymorphism

Reactive arthritis after pharyngeal infection: report of two siblings

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