+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes

HLA-Class I Sensitized Renal Transplant Patients have Antibody Binding to SLA-Class I Epitopes

Transplantation 2019

Highly sensitized patients are difficult to match with suitable renal allograft donors and may benefit from xenotransplant trials. We evaluate antibody binding from sensitized patients to pig cells and engineered single allele cells to identify anti-HLA antibody cross-species reactivity with swine leukocyte antigen (SLA). These novel testing strategies assess HLA/SLA epitopes and antibody binding patterns and introduce genetic engineering of SLA epitopes. Sensitized patient sera was grouped by calculated panel reactive antibody (cPRA) and luminex single antigen reactivity profile and was tested with cloned GGTA1/CMAH/B4GalNT2 glycan knockout (KO) porcine cells. Pig reactivity was assessed by direct flow cytometric crossmatch (FCXM) and studied following elution from pig cells. To study antigenicity of individual Class I HLA and SLA alleles in cells, irrelevant sera binding to lymphoblastoid cells was minimized by CRISPR/Cas9 elimination of endogenous Class I and Class II HLA, b-cell receptor, and Fc-receptor genes. Native HLA, SLA, and mutants of these proteins after mutating 144K to Q were assessed for antibody binding. Those with predominately anti-HLA-B&C antibodies, including Bw6 and Bw4 sensitization, frequently have low pig reactivity. Conversely, antibodies eluted from porcine cells are more commonly anti-HLA-A. Single HLA/SLA antigen expressing engineered cells show variable antigenicity and mutation of 144K-to-Q reduces antibody binding for some sensitized patients. Anti-HLA antibodies cross-react with SLA Class I in predictable patterns which can be identified with histocompatibility strategies and SLA Class I is a possible target of genetic engineering.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 066660465

Download citation: RISBibTeXText

PMID: 30951017

Related references

Diagnosis And Treatment Of Acute Rejection Caused By Donor Specific Anti-Mica Antibody In A Highly Sensitized, Pediatric Renal Transplant Recipient (Major-Histocompatibility-Complex (Mhc) Class-I Related Chain A Antigen). Transplantation 86(Suppl.): 622-623, 2008

Identification of antibodies toward private and public class I HLA epitopes in sensitized patients. Infusionstherapie und Transfusionsmedizin 21(5): 327-332, 1994

Localization of antibody binding epitopes on hla class ii molecules. FASEB Journal 3(3): A793, 1989

A limited number of HLA-epitopes are recognized from HLA class I antibodies detected in the serum of sensitized patients. Human Immunology 60(Suppl. 1): S13, 1999

Epitope analysis of HLA class I donor specific antibodies in sensitized renal transplant recipients. Transplantation 70(2): 323-327, 2000

A limited number of HLA epitopes are recognized from HLA class I-specific antibodies detected in the serum of sensitized patients. Human Immunology 61(7): 705-710, 2000

Predicting promiscuous antigenic T cell epitopes of Mycobacterium tuberculosis mymA operon proteins binding to MHC Class I and Class II molecules. Infection, Genetics and Evolution 44: 182-189, 2017

Human MHC class I transgenic mice deficient for H2 class I expression facilitate identification and characterization of new HLA class I-restricted viral T cell epitopes. Journal of Immunology 169(10): 5571-5580, 2002

Identification of HLA antibodies in renal transplant recipients using class I and class II flow PRA beads. Human Immunology 59(Suppl. 1): 129, 1998

Functional epitope analysis of the human cd4 molecule the mhc class ii dependent activation of resting t cells is inhibited by monoclonal antibodies to cd4 regardless whether or not they recognize epitopes involved in the binding of mhc class ii or hiv gp120. Journal of Immunology 145(9): 2839-2845, 1990

Detection of HLA class I and class II specific antibodies by flow cytometry in renal transplant candidates. Human Immunology 61(Suppl 1): S50, 2000

Detection of HLA class I- and class II-specific antibodies by flow cytometry and PRA-STAT screening in renal transplant recipients. Transplantation 63(12): 1828-1832, 1997

Anti class i antibody is pathogenic in early renal transplant rejections. Clinical & Investigative Medicine 12(Suppl. 4): B75, 1989

Influence of anti-MHC class II antibody and MHC class II binding peptide treatments on interleukin-6 gene expression by B lymphocytes. FASEB Journal 12(5): A1081, 1998

HLA class II antibodies in highly sensitized patients awaiting renal transplantation. Human Immunology 47(1-2): 130, 1996