Open MHC Class I Conformers: A Look through the Looking Glass.

Fernando A Arosa,André J Esgalhado,Elsa M Cardoso,Débora Reste-Ferreira

doi:10.3390/ijms22189738

Fernando A Arosa, André J Esgalhado + Show 2 more

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https://doi.org/10.3390/ijms22189738

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Abstract

Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis–trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with β2m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication.

Highlights

Classical Major Histocompatibility Complex class I (MHC-I) molecules (HLA-A, HLAB, and HLA-C in humans; H-2D, H-2K, and H-2L in mice) have a long past full of ins and outs and untold stories
Binding of luteinizing hormone to its receptor triggers an association with H-2 class I molecules in Leydig cells
This study showed that the anti-HLA-I antibodies had, like sHLA-I conformers, inhibitory activity against virusspecific and allogeneic cytotoxic CD8+ T cells

Summary

Introduction

Classical Major Histocompatibility Complex class I (MHC-I) molecules (HLA-A, HLAB, and HLA-C in humans; H-2D, H-2K, and H-2L in mice) have a long past full of ins and outs and untold stories. They were initially identified as antigens involved in tissue rejection in mice and transfusion-related comorbidities in humans and, called transplantation antigens [1]. Biochemical and molecular biology studies revealed that human and mouse classical MHC-I molecules present at the plasma membrane are trimeric structures formed by a heavy chain of about 45 kDa (thereafter, αHC), non-covalently associated with a 12 kDa beta2-microglobulin light chain (thereafter, β2m), and an 8–12 amino acid peptide.

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