Table I.

Some approaches to predicting HLA-DR peptide binding

Approach	Name	Notes	References
Endogenous peptide sequences	SYFPEITHI	Preferred residues at particular positions	[1]
IC50 assay of single amino acid variants of test peptides	TEPITOPE ProPred	Includes “virtual” matrices for some alleles by pocket combination	[2, 3]
IC50 assay of large sets of varied peptide sequences	ARB, SMM - align	Position-specific scoring matrices	[4, 5]
Analysis of known T cell epitopes	RANKPEP	Position-specific scoring matrices	[6]
Analysis of known T cell epitopes	MULTIPRED	Neural network and Hidden Markov model algorithms, identification of promiscuous epitopes	[7]
Direct binding of peptide displayed on a phage libraries	“anchor combination”	Position-specific scoring matrices	[8]
Binding inhibition by a positional scanning libraries	“undecapeptide library screen”	10-residue motif developed	[9]
Known T cell epitopes, MHC structures and sequences	NetMHCIIPan	Neural network approach to associate binding preferences and MHC sequences	[10]

^[1]Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999; 50:213-9.

^[2]Sturniolo T, Bono E, Ding J, Raddrizzani L, Tuereci O, Sahin U, et al. Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat Biotechnol. 1999; 17:555-61.

^[3]Singh H, Raghava GP. ProPred: prediction of HLA?DR binding sites. Bioinformatics. 2001; 17:1236-7.

^[4]Bui HH, Sidney J, Peters B, Sathiamurthy M, Sinichi A, Purton KA, et al. Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics. 2005; 57:304-14.

^[5]Nielsen M, Lundegaard C, Lund O. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method. BMC Bioinformatics. 2007; 8:238.

^[6]Reche PA, Glutting JP, Reinherz EL. Prediction of MHC class I binding peptides using profile motifs. Hum Immunol. 2002; 63:701-9.

^[7]Zhang GL, Khan AM, Srinivasan KN, August JT, Brusic V. MULTIPRED: a computational system for prediction of promiscuous HLA binding peptides. Nucleic Acids Res. 2005; 33:W172-9.

^[8]Hammer J, Belunis C, Bolin D, Papadopoulos J, Walsky R, Higelin J, et al. High-affinity binding of short peptides to major histocompatibility complex class II molecules by anchor combinations. Proc Natl Acad Sci U S A. 1994; 91:4456-60.

^[9]Fleckenstein B, Kalbacher H, Muller CP, Stoll D, Halder T, Jung G, et al. New ligands binding to the human leukocyte antigen class II molecule DRB1*0101 based on the activity pattern of an undecapeptide library. Eur J Biochem. 1996; 240:71-7.

^[10]Nielsen M, Lundegaard C, Blicher T, Peters B, Sette A, Justesen S, et al. Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan. PLoS Comput Biol. 2008; 4:e1000107.