HLA Class II Presentation Is Specifically Altered at Elevated Temperatures in the B-Lymphoblastic Cell Line JY

Human leukocyte antigen (HLA) molecules play critical roles in our adaptive immune system by signaling a cell's health status to the immune system, through presentation of small peptides. Understanding HLA biology is important because of its prominent role in autoimmune diseases and cancer immunotherapy. Although both the HLA class I and class II antigen processing and presentation pathways have been studied extensively, the fundamental rules in HLA class II antigen presentation still remain less understood. To clarify the mechanistic and adaptive differences between the HLA systems, we challenged a B lymphoblastic cell line (JY), widely used as model system in studying antigen presentation, with a high temperature treatment to mimic a "fever-like state", representing one of the most common physiological responses to infection. In the absence of real invading pathogenic peptides to present, we could focus on delineating the intrinsic HLA pathway adaptations in response to high temperature in this particular cell line. Following a three-pronged approach, we performed quantitative analyses of the proteome, the HLA class I ligandome, as well as the HLA class II ligandome. The data reveals that elevated temperature may already prepare these cells for an immune-like response through increased HLA class II presentation capacity and specific release of, from the invariant chain originating, CLIP peptides. Interestingly, at high temperature, prominent changes in the composition of the CLIP repertoire were observed, with enrichment of peptides containing C-terminal extensions beyond the CLIP-core region. Collectively, these illustrate intriguing temperature sensitive adaptations in this B cell line.