Evaluating the immunogenicity of protein drugs by applying in vitro MHC binding data and the immune epitope database and analysis resource.
The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic features of different prediction methods, the objective evaluation of prediction quality, and general guidelines for practical use of these tools. Finally the use, advantages, and limitations of the methodology will be demonstrated in a review of two previous studies investigating the immunogenicity of erythropoietin and timothy grass pollen.
La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA 92037, USA.
Sinu
S
Paul
Ravi V
RV
Kolla
John
J
Sidney
Daniela
D
Weiskopf
Ward
W
Fleri
Yohan
Y
Kim
Bjoern
B
Peters
Alessandro
A
Sette
D030562:Databases, Protein; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use
D000939:Epitopes; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D004364:Pharmaceutical Preparations; D011506:Proteins