Abstract
Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DRβ1*0402 and DRβ1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4+ T cell line from the DRβ1*0402+ patient PV9 was stimulated by Dsg3 with DRβ1*0402+ L cells as antigen-presenting cells. A CD4+ T cell line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T cell clones from the DR11+ healthy donor C6, required DR11/ DQβ1*0301+ peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting cells and were strongly inhibited by anti-DQ antibodies, indicating that they were restricted by HLA-DQβ1*0301. A CD4+ T cell line and three T cell clones from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRβ1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRβ1*0402, and by HLA-DQβ1*0301.
| Original language | English |
|---|---|
| Pages (from-to) | 388-392 |
| Number of pages | 5 |
| Journal | Journal of Investigative Dermatology |
| Volume | 110 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1998 |
| Externally published | Yes |
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Keywords
- Autoreactivity
- Desmosome
- MHC II
- T lymphocytes
ASJC Scopus subject areas
- Dermatology
Cite this
Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals. / Hertl, M.; Karr, R. W.; Amagai, Masayuki; Katz, S. I.
In: Journal of Investigative Dermatology, Vol. 110, No. 4, 1998, p. 388-392.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals
AU - Hertl, M.
AU - Karr, R. W.
AU - Amagai, Masayuki
AU - Katz, S. I.
PY - 1998
Y1 - 1998
N2 - Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DRβ1*0402 and DRβ1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4+ T cell line from the DRβ1*0402+ patient PV9 was stimulated by Dsg3 with DRβ1*0402+ L cells as antigen-presenting cells. A CD4+ T cell line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T cell clones from the DR11+ healthy donor C6, required DR11/ DQβ1*0301+ peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting cells and were strongly inhibited by anti-DQ antibodies, indicating that they were restricted by HLA-DQβ1*0301. A CD4+ T cell line and three T cell clones from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRβ1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRβ1*0402, and by HLA-DQβ1*0301.
AB - Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DRβ1*0402 and DRβ1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4+ T cell line from the DRβ1*0402+ patient PV9 was stimulated by Dsg3 with DRβ1*0402+ L cells as antigen-presenting cells. A CD4+ T cell line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T cell clones from the DR11+ healthy donor C6, required DR11/ DQβ1*0301+ peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting cells and were strongly inhibited by anti-DQ antibodies, indicating that they were restricted by HLA-DQβ1*0301. A CD4+ T cell line and three T cell clones from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DRβ1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DRβ1*0402, and by HLA-DQβ1*0301.
KW - Autoreactivity
KW - Desmosome
KW - MHC II
KW - T lymphocytes
UR - http://www.scopus.com/inward/record.url?scp=0031945238&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031945238&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1747.1998.00156.x
DO - 10.1046/j.1523-1747.1998.00156.x
M3 - Article
VL - 110
SP - 388
EP - 392
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 4
ER -