Association of MHC and rheumatoid arthritis: Association of RA with HLA-DR4 - the role of repertoire selection
Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. These alleles share a common amino acid motif in their third hypervariable regions: the shared epitope. In normals and patients with RA, HLA-DR genes exert a major influence on the CD4 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 αβ T-cells. However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 αβ T-cell repertoire in RA patients. Shared epitope positive HLA-DR alleles may shape the T-cell repertoire by presenting self peptides to CD4 T cells in the thymus. Peptides processed from HLA-DR molecules and encompassing the shared epitope may also be presented by HLA-DQ and select CD4 αβ T cells in the thymus. Thus, shared epitope-positive alleles impose a frame on the T-cell repertoire. This predisposing frame is further modified (by unknown factors) to obtain the contracted rheumatoid repertoire.
Complete Metadata
| @type | dcat:Dataset |
|---|---|
| accessLevel | public |
| bureauCode |
[
"009:25"
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|
| contactPoint |
{
"fn": "NIH",
"@type": "vcard:Contact",
"hasEmail": "mailto:info@nih.gov"
}
|
| description | Most patients with rheumatoid arthritis (RA) express HLA-DR4, HLA-DR1 or HLA-DR10. These alleles share a common amino acid motif in their third hypervariable regions: the shared epitope. In normals and patients with RA, HLA-DR genes exert a major influence on the CD4 αβ T-cell repertoire, as shown by studies of AV and BV gene usage and by BV BJ gene usage by peripheral blood CD4 αβ T-cells. However, the rheumatoid T-cell repertoire is not entirely under HLA-DR influence, as demonstrated by discrepancies in VB JB gene usage between identical twins discordant for RA and by contraction of the CD4 αβ T-cell repertoire in RA patients. Shared epitope positive HLA-DR alleles may shape the T-cell repertoire by presenting self peptides to CD4 T cells in the thymus. Peptides processed from HLA-DR molecules and encompassing the shared epitope may also be presented by HLA-DQ and select CD4 αβ T cells in the thymus. Thus, shared epitope-positive alleles impose a frame on the T-cell repertoire. This predisposing frame is further modified (by unknown factors) to obtain the contracted rheumatoid repertoire. |
| distribution |
[
{
"@type": "dcat:Distribution",
"title": "Official Government Data Source",
"mediaType": "text/html",
"description": "Visit the original government dataset for complete information, documentation, and data access.",
"downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC130006/"
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|
| identifier | https://healthdata.gov/api/views/jfx7-rdvs |
| issued | 2025-07-14 |
| keyword |
[
"hla-dr4",
"nih",
"rheumatoid-arthritis",
"shared-epitope",
"t-cell-repertoire"
]
|
| landingPage | https://healthdata.gov/d/jfx7-rdvs |
| modified | 2025-09-06 |
| programCode |
[
"009:048"
]
|
| publisher |
{
"name": "National Institutes of Health",
"@type": "org:Organization"
}
|
| theme |
[
"NIH"
]
|
| title | Association of MHC and rheumatoid arthritis: Association of RA with HLA-DR4 - the role of repertoire selection |
