Class II-associated invariant chain peptide (CLIP) (CLIP)

Class II-associated invariant chain peptide (CLIP) is a peptide fragment derived from the CD74 protein that occupies the antigen-binding groove of MHC class II molecules during their intracellular assembly and transport [3, 12]. In healthy physiological states, CLIP is typically exchanged for exogenous antigenic peptides by the chaperone HLA-DM before the MHC II complex is presented on the cell surface to CD4+ T cells [3, 7]. However, in various pathological conditions—including preeclampsia, certain cancers, and autoimmune disorders—CLIP remains bound to MHC II and is expressed on the cell surface [2, 5]. This ectopic surface expression of CLIP serves as a ligand for specific subsets of gamma delta (γδ) T cells, which can trigger pro-inflammatory cascades or contribute to immune dysfunction [1, 2]. Therapeutic interventions, such as the competitive antagonist peptide VG1177, aim to displace CLIP from the MHC II groove to prevent the activation of pathogenic γδ T cells and restore immune homeostasis [2, 13]. Modulating this interaction represents a novel approach for treating inflammatory and immune-mediated diseases by targeting the transition between innate and adaptive immunity [1, 6].

Other names

MHCII-CLIP complexCD74 fragmentMHC class II invariant chain peptideEctopic CLIP

Competitive inhibition of CLIP binding to the MHC class II groove, leading to the displacement of CLIP and subsequent modulation of gamma delta T cell and regulatory T cell (Treg) activity.