What thresholds (cut-offs) should I use for MHC class I and II binding predictions – IEDB Solutions Center

MHC class I

For MHC class I T cell epitope predictions, selection of predicted binders can be done based on the percentile rank or MHC binding affinity. The IEDB currently recommends making selections based on a percentile rank of <= 1% for each (MHC allele, length) combination to cover most of the immune responses.^{1, 2} Alternatively, a binding affinity (IC50) threshold of 500 nM identifies peptide binders recognized by T cells and this threshold can be used to select peptides.³Recently, a paper from our group showed that absolute binding affinity threshold correlates better with immunogenicity and also that, for even better correlation, MHC-specific thresholds should be used.⁴ The tables below show the allele-specific thresholds for the 38 most common HLA-A and HLA-B alleles, representative of the nine major supertypes. The tables can also be downloaded as an RTF file (see attached file).

Alleles sorted by population frequency			Alleles sorted by name
Allele	Population frequency of allele	Allele specific affinity cutoff (IC50 nM)	Allele	Population frequency of allele	Allele specific affinity cutoff (IC50 nM)
A*0201	25.2	255	A*0101	16.2	884
A*2402	16.8	849	A*0201	25.2	255
A*0101	16.2	884	A*0203	3.3	92
A*0301	15.4	602	A*0206	4.9	60
B*0702	13.3	687	A*0301	15.4	602
A*1101	12.9	382	A*1101	12.9	382
B*0801	11.5	663	A*2301	6.4	740
B*4001	10.3	639	A*2402	16.8	849
B*4402	9.2	904	A*2501	2.5	795
B*4403	7.6	780	A*2601	4.7	815
B*3501	6.5	348	A*2902	2.9	641
A*2301	6.4	740	A*3001	5.1	109
A*3201	5.7	131	A*3002	5	674
B*5101	5.5	939	A*3101	4.7	329
B*5301	5.4	538	A*3201	5.7	131
B*1501	5.2	528	A*3301	3.2	606
A*3001	5.1	109	A*6801	4.6	197
A*3002	5	674	A*6802	3.3	259
A*0206	4.9	60	B*0702	13.3	687
A*3101	4.7	329	B*0801	11.5	663
A*2601	4.7	815	B*1402	2.8	700
A*6801	4.6	197	B*1501	5.2	528
B*1801	4.4	732	B*1801	4.4	732
B*4601	4	926	B*2705	2	584
B*5801	3.6	446	B*3501	6.5	348
B*4002	3.5	590	B*3503	1.2	888
A*6802	3.3	259	B*3801	2	944
A*0203	3.3	92	B*3901	2.9	542
A*3301	3.2	606	B*4001	10.3	639
B*5701	3.2	716	B*4002	3.5	590
A*2902	2.9	641	B*4402	9.2	904
B*3901	2.9	542	B*4403	7.6	780
B*1402	2.8	700	B*4601	4	926
A*2501	2.5	795	B*4801	1.8	887
B*2705	2	584	B*5101	5.5	939
B*3801	2	944	B*5301	5.4	538
B*4801	1.8	887	B*5701	3.2	716
B*3503	1.2	888	B*5801	3.6	446

MHC class II

For MHC class II T cell epitope predictions, selection of predicted binders can be done based on the percentile rank or MHC binding affinity. The IEDB currently recommends making selections based on a consensus percentile rank of the top 10%. Alternatively, selecting peptides predicted to bind at 1,000nM is also supported by experimental data⁵ [(Southwood, Sidney et al. 1998)]. In addition to using IEDB generated percentile rank and MHC binding affinity, other alternate approaches for selecting binders can also be utilized depending on a user’s needs. For example, if there are too few or too many predicted binders based on the recommended threshold, and the user needs more or fewer peptides to study, it is advisable to vary the cut-off values and select the desired number of top scoring peptides. Another scenario may be to set a desired percentage within the user’s peptide set (irrespective of IEDB percentile rank), if it is desired to study a fixed number of the best predicted peptides^.

Moutftsi et al., 2006, Nat. Biotech (PMID 16767078)
Kotturi et al., 2007, J. Virology (PMID 17329346)
Sette et al., 1994, J. Immunology (PMID 7527444)
Paul et al., 2013, J. Immunology (PMID 24190657)
Southwood et al., 1998, J. Immunology (PMID 9531296)

class_I_allele_specific_cutoff.rtf
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