Abundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome

Adaptive
cellular and humoral immune responses to infectious agents
require previous recognition of pathogenic peptides bound to human
leukocyte antigen (HLA) class II molecules exposed on the surface
of the professional antigen-presenting cells. Knowledge of how these
peptide ligands are generated is essential to understand the basis
for CD4+ T-cell-mediated immunity and tolerance. In this
study, a high-throughput mass spectrometry analysis was used to identify
more than 16,000 cell peptides bound to several HLA-DR and -DP class
II molecules isolated from large amounts of uninfected and virus-infected
human cells (ProteomeXchange accession: PXD028006). The analysis of
the 1808 parental proteins containing HLA class II ligands revealed
that these cell proteins were more acidic, abundant, and highly connected
but less hydrophilic than non-parental proteomes. Therefore, the percentage
of acidic residues was increased and hydroxyl and polar residues were
decreased in the parental proteins for the HLA class II ligandomes
versus the non-parental proteomes. This definition of the properties
shared by parental proteins that constitute the source of the HLA
class II ligandomes can serve as the basis for the development of
bioinformatics tools to predict proteins that are most likely recognized
by the immune system through the CD4+ helper T lymphocytes
in both autoimmunity and infection.