Citations 3
Author response: Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity
Yarzabek, Brogan , Olson, Eli , Silva, Gayathri N. , Geretz, Aviva , Thomas, Rasmi , Krishnakumar, Sujatha , Ramón, Daniel S. , Zaitouna, Anita , Geng, Jie , Raghavan, Malini
No container title available | July 10, 2018 | Volume: No volume available | Issue: No issue available | Pages: No page available
Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity
Yarzabek, Brogan , Zaitouna, Anita , Olson, Eli , Silva, Gayathri N. , Geng, Jie , Geretz, Aviva , Thomas, Rasmi , Krishnakumar, Sujatha , Ramón, Daniel S. , Raghavan, Malini , Zaitouna, Anita J , Raghavan, Malini
eLife | July 10, 2018 | Volume: 7 | Issue: No issue available | Pages: No page available
The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by peptide loading complex (PLC) components is expected to ensure the cell surface expression of stable peptide-HLA class I complexes. This is exemplified by HLA-B*08:01 in primary human lymphocytes, with both expression level and half-life at the high end of the measured HLA-B expression and stability hierarchies. Conversely, low expression on lymphocytes is measured for three HLA-B allotypes that bind peptides with proline at position 2, which are disfavored by the transporter associated with antigen processing. Surprisingly, these lymphocyte-specific expression and stability differences become reversed or altered in monocytes, which display larger intracellular pools of HLA class I than lymphocytes. Together, the findings indicate that allele and cell-dependent variations in antigen acquisition pathways influence HLA-B surface expression levels, half-lives and receptivity to exogenous antigens.
Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology
Wang, Sophia , Abdou, Amr M. , Morton, Lindsay M. , Thomas, Rasmi , Cerhan, James R. , Gao, Xiaojiang, Rothman, Nathaniel , Severson, Richard K., Hartge, Patricia, Carrington, Mary , Cozen, Wendy , Davis, Scott , Bernstein, Leslie , Cerhan, James R , Morton, Lindsay M , Wang, Sophia S
Blood | April 13, 2010 | Volume: 115 | Issue: 23 | Pages: 4820-4823
AbstractGenome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.