{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:53:28Z","timestamp":1760151208703,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Serum anti-HLA-I IgG are present in non-alloimmunized males, cancer patients, and transplant recipients. Anti-HLA-I antibodies are also present in intravenous immunoglobulin (IVIg), prepared from the plasma of thousands of healthy donors. However, the HLA-Ia reactivity of IVIg diminishes markedly after passing through HLA-E HC-affinity columns, suggesting that the HLA-I reactivity is due to antibodies formed against HLA-E. Hence, we examined whether anti-HLA-E antibodies can react to HLA-I alleles. Monoclonal IgG antibodies (mAbs) against HCs of two HLA-E alleles were generated in Balb\/C mice. The antibodies were analyzed using multiplex bead assays on a Luminex platform for HLA-I reactivity. Beads coated with an array of HLA heterodimers admixed with HCs (LABScreen) were used to examine the binding of IgG to different HLA-Ia (31-HLA-A, 50-HLA-B, and 16-HLA-C) and Ib (2-HLA-E, one each of HLA-F and HLA-G) alleles. A striking diversity in the HLA-Ia and\/or HLA-Ib reactivity of mAbs was observed. The number of the mAbs reactive to (1) only HLA-E (n = 25); (2) all HLA-Ib isomers (n = 8); (3) HLA-E and HLA-B (n = 5); (4) HLA-E, HLA-B, and HLA-C (n = 30); (5) HLA-E, HLA-A*1101, HLA-B, and HLA-C (n = 83); (6) HLA-E, HLA-A, HLA-B, and HLA-C (n = 54); and (7) HLA-Ib and HLA-Ia (n = 8), in addition to four other minor groups. Monospecificity and polyreactivity were corroborated by HLA-E monospecific and HLA-I shared sequences. The diverse HLA-I reactivity of the mAbs are compared with the pattern of HLA-I reactivity of serum-IgG in non-alloimmunized males, cancer patients, and ESKD patients. The findings unravel the diagnostic potential of the HLA-E monospecific-mAbs and immunomodulatory potentials of IVIg highly mimicking HLA-I polyreactive-mAbs.<\/jats:p>","DOI":"10.3390\/antib11010018","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T22:53:25Z","timestamp":1646261605000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ramifications of the HLA-I Allelic Reactivity of Anti-HLA-E*01:01 and Anti-HLA-E*01:03 Heavy Chain Monoclonal Antibodies in Comparison with Anti-HLA-I IgG Reactivity in Non-Alloimmunized Males, Melanoma-Vaccine Recipients, and End-Stage Renal Disease Patients"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5731-4129","authenticated-orcid":false,"given":"Mepur H.","family":"Ravindranath","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Children\u2019s Hospital, Los Angeles, CA 90027, USA"},{"name":"Emeritus Research Scientist at Terasaki Foundation Laboratory, Santa Monica, CA 90064, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narendranath M.","family":"Ravindranath","sequence":"additional","affiliation":[{"name":"Norris Dental Science Center, Herman Vostro School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-5353","authenticated-orcid":false,"given":"Fatiha","family":"El Hilali","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy of Laayoune, Ibn Zohr University, Agadir 70000, Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senthamil R.","family":"Selvan","sequence":"additional","affiliation":[{"name":"Tetracore Inc., Rockville, MD 20850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward J.","family":"Filippone","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19145, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev.iy.07.040189.003125","article-title":"Antigen recognition by class I-restricted T lymphocytes","volume":"7","author":"Townsend","year":"1989","journal-title":"Ann. 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