Novel insights into MHC-I function using CRISPR/Cas9 screens

Abstract

Major Histocompatibility Complex (MHC) molecules, also called human leukocyte antigens (HLA), are crucial players in the adaptive immune system, as they are the ligands of the T cell receptor (TCR), and enable T-cells to distinguish unhealthy cells from healthy ones. While MHC class II molecules present peptides derived from extracellular sources on the cell surface, MHC class I molecules present intracellular peptides, hereby portraying the intracellular status to the extracellular environment. Naïve CD4 T cells recognize antigens in the context of MHC-II to differentiate into multiple types of helper T cells, including T follicular

helper cells that promote the B cell response. Naïve CD8+ T cells recognize antigens in the context of MHC-I and then differentiate into cytotoxic T cells that can lyse their target

cells. Besides the interaction with the TCR, MHC-I engages in additional interactions with other receptors, including LILRs and KIRs to regulate immune function on multiple levels. This variety of interactions grants MHC-I the ability to regulate multiple elements of the immune system simultaneously. This thesis is focused on MHC-I and related molecules.