A new categorization of HLA DR alleles on a functional basis

Ou, Dawei; Mitchell, Leslie A.; Tingle, Aubrey J.

doi:10.1016/s0198-8859(98)00067-6

Cited by 72 publications

(85 citation statements)

References 87 publications

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“…in different HLA class I supertypes is frequent. However, further analyses also indicated that the present data do not warrant alternative classifications of HLA class I alleles into allelic groups that are guided by functional rather than sequence or binding motif similarities, as has been proposed for HLA class II alleles [20]. Nevertheless, the currently available data may help to better define the structural flexibility of different epitopebinding pocket interactions and to confirm previous studies showing that residues flanking the traditional binding positions can also affect the ability of specific epitopes to bind to their restricting HLA alleles(s) [10,[43][44][45].…”

Section: Discussioncontrasting

confidence: 61%

“…Given the relatively well-established class I binding motifs for at least some alleles, and in strong contrast to the binding promiscuity for MHC class II-restricted epitopes [15][16][17][18][19][20][21], binding of epitopes across a broad spectrum of HLA class I alleles has been considered the exception rather than the rule [22,23]. Yet, some similarities between different binding motifs exist, and promiscuous presentation of epitopes to a certain degree could be expected [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Extensive HLA class I allele promiscuity among viral CTL epitopes

et al. 2007

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Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development.

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Section: Discussioncontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Extensive HLA class I allele promiscuity among viral CTL epitopes

et al. 2007

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“…HLA-DR15 molecules derived from DRB1*1502 differ from those derived from DRB1*1501 in only one amino acid at position 86 (valine for DRB1*1502 and glycine for DRB1*1501) of the beta-chain [31]. This structural similarity indicates that antigenic epitopes presented by these molecules are common [32,33]. For most autoimmune diseases where DRB1*1501 is associated with susceptibility in patients from Western countries, DRB1*1502 is expected to play the same role as DRB1*1501 in Japanese patients.…”

Section: Discussionmentioning

confidence: 97%

Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Sugimori

Yamazaki

Feng

et al. 2007

Experimental Hematology

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Category Clinical investigations Word countsTotal text word count: 3412 words Abstract word count: 240 words 2 ABSTRACTObjective. Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1*1501 and DRB1*1502, the 2 DRB1 alleles which determine the presentation of HLA-DR15, in the pathophysiology of AA. Materials and Methods.We investigated the relationships of the patients' HLA-DRB1 allele with both the presence of a small population of CD55 -CD59 -(PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporine (CsA) therapy in 140 Japanese AA patients. Results. Of the 30 different DRB1 alleles, only DRB1*1501 (33.6% vs. 12.8%, P c <0.01) and DRB1*1502 (43.6% vs. 24.4%, P c <0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1*1502 in patients ≥40 years old (52.4%) was markedly higher than that in those <40 years old (16.2%, P c <0.01). Only DRB1*1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (P<0.01). Conclusion.Although both DRB1*1501 and DRB1*1502 contribute to the development of AA, the methods of contribution differ between the two alleles.3

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“…Además del fundamento epidemiológico de la hipótesis del SE, Ou et al (112) introdujeron una clasificación funcional de los alelos HLA-DR sustentada por la evidencia experimental de la restricción-DR del receptor de células T (TCR). Dicha categorización establece siete patrones de supertipo DR-restrictivo (RSP) según los residuos polimórficos β70, β71 y β74 del HLA-DR, aminoácidos que se unen al péptido durante la presentación antigénica y entran en contacto con el TCR, por lo cual le confieren la especificidad a la molécula, modelan el repertorio de linfocitos T, y determinan la asociación con susceptibilidad o resistencia a enfermedades (cuadro 7).…”

Section: Figura 2 Complejo Mayor De Histocompatibilidadunclassified

“…0801 1301 1101 Posición 0404 0301 0403 1501 0802 1302 0101 1104 del aa 0401 0405 1001 1402 0302 0406 0901 1401 1502 1601 0701 0803 1201 1303 1309 0402 0103 1304 0102 1106 en DRb 0408 1109 0407 1503 0804 1102 1305 0805 1103 Los alelos de susceptibilidad asociados con artritis reumatoide codifican la secuencia del RSP "A" ( 70 Q/R 71 R 74 K/A); en contraste, los RSP "De" ( 70 D 71 E/T 74 A) y "E" ( 70 Q/R 71 R 74 E), codificados por los alelos DRB1*0402 (De), *0403 y *0407 (E), están reportados como factores protectores para la enfermedad (112). Esta observación es coherente con el efecto protector atribuido a varios alelos HLA-DRB1 (*0103, *0402, *1102, *1103, *1301, *1302 y *1304), los cuales comparten la secuencia 70 DERAA 74 en vez del SE (113,114).…”

Section: Cuadrounclassified

Epidemiología genética de la artritis reumatoide: ¿qué esperar de América Latina?

et al. 2011

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La artritis reumatoide es una enfermedad sistémica autoinmune, crónica, que afecta principalmente las articulaciones que tienen movimiento. La enfermedad es mucho más frecuente en mujeres y su prevalencia en la población latinoamericana es cercana al 0,5%. La existencia de agregación familiar (λ s = 2-17) indica su carácter hereditario. Sin embargo, la herencia de la artritis reumatoide es poligénica y no sigue un patrón mendeliano. La importancia de encontrar factores genéticos asociados con la artritis reumatoide radica en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, su posible aplicación clínica como marcadores de riesgo, diagnóstico, pronóstico, e incluso, blanco terapéutico. Mapeos genéticos llevados a cabo en diversas poblaciones en busca de loci y genes candidatos han identificado la región HLA como aquella con mayor evidencia de ligamento. Sin embargo, su fracción etiológica corresponde sólo a un tercio de la susceptibilidad genética de la enfermedad. Esto indica que genes diferentes al HLA también están implicados en la susceptibilidad a desarrollar artritis reumatoide. En Latinoamérica, los alelos HLA-DRB1*0404 y TNF -308A han sido asociados de manera uniforme con la artritis reumatoide. En el presente artículo se revisan los factores genéticos de la artritis reumatoide en el marco de una aproximación lógica y ordenada establecida por la epidemiología genética, y se ofrecen algunas recomendaciones para futuros estudios en poblaciones latinoamericanas.Palabras clave: artritis reumatoide, epidemiología, enfermedades autoinmunes, complejo mayor de histocompatibilidad, antígenos HLA, América Latina. Genetic epidemiology of rheumatoid arthritis: What to expect from Latin America?Rheumatoid arthritis is a chronic and systemic autoimmune disease characterized by inflammation and destruction of the synovial joints. It affects approximately 0.5% of the LatinAmerican population and is three times more common in women than in men. Evidence of familial aggregation (λ s =2-17) was the first indication of a genetic susceptibility to disease. As in other autoimmune diseases, it has a complex genetic basis. Results from whole-genome scans indicate that the HLA region contains a significant and consistent set of linked loci. However, HLA accounts for only one-third of the genetic susceptibility of disease, indicating that non-HLA genes are also involved in the disease susceptibility. In Latin-America, association with HLA-DRB1*0404 and TNF -308A alleles has been uniformly established; however, many other candidate genes remain to be studied. The identification of genetic factors conferring susceptibility to rheumatoid arthritis will contribute to the knowledge of the pathogenic mechanisms, ability to predict its occurrence, the development of diagnostic tools, prognosis, and treatment. The genetic epidemiology of rheumatoid arthritis is herein reviewed; a set of recommendations is provided for the design, analysis and interpretation of genetic association studies in the context of La...

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A new categorization of HLA DR alleles on a functional basis

Cited by 72 publications

References 87 publications

Extensive HLA class I allele promiscuity among viral CTL epitopes

Extensive HLA class I allele promiscuity among viral CTL epitopes

Roles of DRB1∗1501 and DRB1∗1502 in the pathogenesis of aplastic anemia

Epidemiología genética de la artritis reumatoide: ¿qué esperar de América Latina?

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