%0 Journal Article %1 Rottembourg2010 %A Rottembourg, Diane %A Deal, Cheri %A Lambert, Marion %A Mallone, Roberto %A Carel, Jean-Claude %A Lacroix, André %A Caillat-Zucman, Sophie %A le Deist, Françoise %D 2010 %J J Autoimmun %K chemistry/immunology;Polyendocrinopathies secretion;Male;MiddleAged;PeptideFragments blood;CD8-PositiveT-Lymphocytes T-Lymphocyte diagnosis/immunology/pathology/physiopathology;Adolescent;Adult;Autoantibodies AddisonDisease Autoimmune immunology/metabolism;Humans;Interferon-gamma Cultured;Child;Enzyme-LinkedImmunospotAssay;EpitopeMapping;Epitopes chemistry/immunology;Female;HLA-B8Antigen drottembourg diagnosis/immunology/pathology/physiopathology;Steroid21-Hydroxylase immunology/metabolism/pathology;Cells chemistry/immunology %N 4 %P 309--315 %R 10.1016/j.jaut.2010.07.001 %T 21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison's disease. %U http://dx.doi.org/10.1016/j.jaut.2010.07.001 %V 35 %X In autoimmune adrenal deficiency, autoantibodies target the 21-hydroxylase (21OH) protein. However, it is presumed that autoreactive T cells, rather than antibodies, are the main effectors of adrenal gland destruction, but their identification is still lacking. We performed a T-cell epitope mapping study using 49 overlapping 20mer peptides covering the 21OH sequence in patients with isolated Addison's disease, Autoimmune Polyendocrine Syndrome 1 and 2. IFNγ ELISPOT responses against these peptides were stronger, broader and more prevalent among patients than in controls, whatever the disease presentation. Five peptides elicited T-cell responses in patients only (68\% sensitivity, 100\% specificity). Blocking experiments identified IFNγ-producing cells as CD8 T lymphocytes, with two peptides frequently recognized in HLA-B8+ patients and a third one targeted in HLA-B35+ subjects. In particular, the 21OH(431-450) peptide was highly immunodominant, as it was recognized in more than 30\% of patients, all carrying the HLA-B8 restriction element. This 21OH(431-450) region contained an EPLARLEL octamer (21OH(431-438)) predicted to bind to HLA-B8 with high affinity. Indeed, circulating EPLARLEL-specific CD8 T cells were detected at significant frequencies in HLA-B8+ patients but not in controls by HLA tetramer staining. This report enlightens disease-specific T-cell biomarkers and epitopes targeted in autoimmune adrenal deficiency.

@article{Rottembourg2010, abstract = {In autoimmune adrenal deficiency, autoantibodies target the 21-hydroxylase (21OH) protein. However, it is presumed that autoreactive T cells, rather than antibodies, are the main effectors of adrenal gland destruction, but their identification is still lacking. We performed a T-cell epitope mapping study using 49 overlapping 20mer peptides covering the 21OH sequence in patients with isolated Addison's disease, Autoimmune Polyendocrine Syndrome 1 and 2. IFNγ ELISPOT responses against these peptides were stronger, broader and more prevalent among patients than in controls, whatever the disease presentation. Five peptides elicited T-cell responses in patients only (68\% sensitivity, 100\% specificity). Blocking experiments identified IFNγ-producing cells as CD8 T lymphocytes, with two peptides frequently recognized in HLA-B8+ patients and a third one targeted in HLA-B35+ subjects. In particular, the 21OH(431-450) peptide was highly immunodominant, as it was recognized in more than 30\% of patients, all carrying the HLA-B8 restriction element. This 21OH(431-450) region contained an EPLARLEL octamer (21OH(431-438)) predicted to bind to HLA-B8 with high affinity. Indeed, circulating EPLARLEL-specific CD8 T cells were detected at significant frequencies in HLA-B8+ patients but not in controls by HLA tetramer staining. This report enlightens disease-specific T-cell biomarkers and epitopes targeted in autoimmune adrenal deficiency.}, added-at = {2011-06-21T22:14:50.000+0200}, author = {Rottembourg, Diane and Deal, Cheri and Lambert, Marion and Mallone, Roberto and Carel, Jean-Claude and Lacroix, André and Caillat-Zucman, Sophie and le Deist, Françoise}, biburl = {https://www.bibsonomy.org/bibtex/2cd05ce24fe877c547d6918412d011751/crc_chus}, doi = {10.1016/j.jaut.2010.07.001}, institution = {Endocrinology Service, CHU Sainte-Justine, Department of Pediatrics, Université de Montréal, H3T 1C5 Montréal, Canada.}, interhash = {e3cfae89291a5b38084265d7a985e12e}, intrahash = {cd05ce24fe877c547d6918412d011751}, journal = {J Autoimmun}, keywords = {chemistry/immunology;Polyendocrinopathies secretion;Male;MiddleAged;PeptideFragments blood;CD8-PositiveT-Lymphocytes T-Lymphocyte diagnosis/immunology/pathology/physiopathology;Adolescent;Adult;Autoantibodies AddisonDisease Autoimmune immunology/metabolism;Humans;Interferon-gamma Cultured;Child;Enzyme-LinkedImmunospotAssay;EpitopeMapping;Epitopes chemistry/immunology;Female;HLA-B8Antigen drottembourg diagnosis/immunology/pathology/physiopathology;Steroid21-Hydroxylase immunology/metabolism/pathology;Cells chemistry/immunology}, language = {eng}, medline-pst = {ppublish}, month = Dec, number = 4, pages = {309--315}, pii = {S0896-8411(10)00076-4}, pmid = {20685079}, timestamp = {2011-06-21T22:14:51.000+0200}, title = {21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison's disease.}, url = {http://dx.doi.org/10.1016/j.jaut.2010.07.001}, volume = 35, year = 2010 }