Title:HLA-I Antigen Presentation and Tapasin Influence Immune Responses Against Malignant Brain Tumors-Considerations for Successful Immunotherapy
Volume: 14
Issue: 8
Author(s): Anna Darabi, Camilla Thuring and Kajsa M. Paulsson
Affiliation:
Keywords:
Brain tumor, cytokine, HLA-I, MHC-I, tapasin.
Abstract: Human leukocyte antigen class I (HLA-I) presents antigenic peptides to cytotoxic CD8+ T cells (CTLs). This is a pivotal step
in the generation of CTL responses. Both the quantity and quality of peptide-HLA-I (pHLA-I) complexes are crucial for CTL responses,
but the level of HLA-I expression per se is also directly involved in dictating NK-cell responses. Antigen processing machinery (APM)
proteins are involved in the maturation of HLA-I and in the selection of which peptides are – or are not – presented. Thus, these proteins
are key players in shaping the immune response to cells in health and disease. In this review, we recap the most important features of
APM components and their synergistic work to assure proper pHLA-I cell surface expression. We pay special attention to the HLA-I
dedicated multifunctional protein, tapasin, and in relation to the different tapasin-dependency of HLA-I allomorphs we also discuss
allomorph specific traits in maturation, structure and linkage to malignant diseases and brain tumors in particular. We next discuss the
possibilities of restoring or manipulating the immune responses against brain tumors. In this context we discuss IFNγ therapy, cytostatics
and irradiation. Finally, we integrate current views and knowledge to set the direction for future emphasis in the area of immunotherapy
against brain tumors.
